Search results for: pathological constriction

Authors: Caroline F. Moeser

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The skin-gut axis defines the relationship between the intestinal microbiota and the development of pathological skin diseases. Low diversity within the gut can predispose to the development of allergic skin conditions, and a greater diversity of the gastrointestinal microflora has been associated with a reduction of skin flares in people with atopic dermatitis. Manipulation of the gut microflora has been used as a treatment option for several conditions in people, but there is limited data available on the use of faecal transplantation as a preventative measure in either people or dogs. Six, 4-month-old pups from a litter of ten were presented for diarrhea and/or signs of skin disease (chronic scratching, otitis externa). Of these pups, two were given probiotics with a resultant resolution of diarrhea. The other four pups were given faecal transplantation, either as a sole treatment or in combination with other treatments. Follow-up on the litter of ten pups was performed at 18 months of age. At this stage, the four pups that had received faecal transplantation had resolved all clinical signs and had no recurrence of either skin or gastrointestinal symptoms. Of the remaining six pups from the litter, all had developed at least one episode of Malassezia otitis externa within the period of 5 months to 18 months of age. Two pups had developed two Malassezia otitis infections, and one had developed three Malassezia otitis infections during this period. Favrot’s criteria for the diagnosis of canine atopic dermatitis include chronic or recurrent Malassezia infections by the age of three years. Early results from this litter predict a reduction in the development of canine atopic disease in dogs given faecal microbial transplantation. Follow-up studies at three years of age and within a larger population of dogs can enhance understanding of the impact of early faecal transplantation in the prevention of canine atopic dermatitis.

Keywords: canine atopic dermatitis, faecal microbial transplant, skin-gut axis, otitis

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Authors: Lina T. Al Kury, Oleg I. Voitychuk, Ramiz M. Ali, Sehamuddin Galadari, Keun-Hang Susan Yang, Frank Christopher Howarth, Yaroslav M. Shuba, Murat Oz

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A role for anandamide (N-arachidonoyl ethanolamide; AEA), a major endocannabinoid, in the cardiovascular system in various pathological conditions has been reported in earlier studies. In the present work, we have hypothesized that the antiarrhythmic effects reported for AEA are due to its negative inotropic effect and altered action potential (AP) characteristics. Therefore, we tested the effects of AEA on contractility and electrophysiological properties of rat ventricular myocytes. Video edge detection was used to measure myocyte shortening. Intracellular Ca2+ was measured in cells loaded with the fluorescent indicator fura-2 AM. Whole-cell patch-clamp technique was employed to investigate the effect of AEA on the characteristics of APs. AEA (1 μM) caused a significant decrease in the amplitudes of electrically-evoked myocyte shortening and Ca2+ transients and significantly decreased the duration of AP. The effect of AEA on myocyte shortening and AP characteristics was not altered in the presence of pertussis toxin (PTX, 2 µg/ml for 4 h), AM251 and SR141716 (cannabinoid type 1 receptor antagonists) or AM630 and SR 144528 (cannabinoid type 2 receptor antagonists). Furthermore, AEA inhibited voltage-activated inward Na+ (INa) and Ca2+ (IL,Ca) currents; major ionic currents shaping the APs in ventricular myocytes, in a voltage and PTX-independent manner. Collectively, the results suggest that AEA depresses ventricular myocyte contractility, by decreasing the action potential duration (APD), and inhibits the function of voltage-dependent Na+ and L-type Ca2+ channels in a manner independent of cannabinoid receptors. This mechanism may be importantly involved in the antiarrhythmic effects of anandamide.

Keywords: action potential, anandamide, cannabinoid receptor, endocannabinoid, ventricular myocytes

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Authors: S. M. Ismail, H-H Yen, C. M. Murray, H. M. S. Davies

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A recent study reported a 33% incidence of complete sacrocaudal fusion in greyhounds compared to a 3% incidence in other dogs. In the dog, the median sacral crest is formed by the fusion of sacral spinous processes. Separation of the 1st spinous process from the median crest of the sacrum in the dog has been reported as a diagnostic tool of type one lumbosacral transitional vertebra (LTV). LTV is a congenital spinal anomaly, which includes either sacralization of the caudal lumbar part or lumbarization of the most cranial sacral segment of the spine. In this study, the absence or reduction of fusion (presence of separation) between the 1st and 2ndspinous processes of the median sacral crest has been identified in association with sacrocaudal fusion in the greyhound, without any feature of LTV. In order to provide quantitative data on the absence or reduction of fusion in the median sacral crest between the 1st and 2nd sacral spinous processes, in association with sacrocaudal fusion. 204 dog sacrums free of any pathological changes (192 greyhound, 9 beagles and 3 labradors) were grouped based on the occurrence and types of fusion and the presence, absence, or reduction in the median sacral crest between the 1st and 2nd sacral spinous processes., Sacrums were described and classified as follows: F: Complete fusion (crest is present), N: Absence (fusion is absent), and R: Short crest (fusion reduced but not absent (reduction). The incidence of sacrocaudal fusion in the 204 sacrums: 57% of the sacrums were standard (3 vertebrae) and 43% were fused (4 vertebrae). Type of sacrum had a significant (p < .05) association with the absence and reduction of fusion between the 1st and 2nd sacral spinous processes of the median sacral crest. In the 108 greyhounds with standard sacrums (3 vertebrae) the percentages of F, N and R were 45% 23% and 23% respectively, while in the 84 fused (4 vertebrae) sacrums, the percentages of F, N and R were 3%, 87% and 10% respectively and these percentages were significantly different between standard (3 vertebrae) and fused (4 vertebrae) sacrums (p < .05). This indicates that absence of spinous process fusion in the median sacral crest was found in a large percentage of the greyhounds in this study and was found to be particularly prevalent in those with sacrocaudal fusion – therefore in this breed, at least, absence of sacral spinous process fusion may be unlikely to be associated with LTV.

Keywords: greyhound, median sacral crest, sacrocaudal fusion, sacral spinous process

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Authors: P. Afsharian, S. Mousazadeh, M. Shahhoseini, R. Aflatoonian

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Introduction: Matrix MetalloProteinases (MMPs) degrade extracellular matrix components to provide normal remodeling and contribute to pathological tissue destruction and cell migration in endometriosis. It is accepted that MMPs are resistant to suppression by progesterone in endometriotic tissues. The physiological effects of progesterone are mediated by its two progesterone receptor (PGR) isoforms, namely PGR-A and PGR-B. The capacity of progesterone affect to gene expression is dependent on the PGR-A/PGR-B ratio. The imbalance ratio in endometriotic tissue may be an important mechanism to be resulted in Progesterone resistance and modify progesterone action via differential regulation of specific progesterone response genes and improve endometriosis disease. Material and methods: RNA was extracted from twenty ectopic (endometriotic) and eutopic (endometrial) tissue samples of women undergoing laparoscopy for endometriosis and 20 healthy fertile women at Royan Institute, Tehran, Iran. Analysis of PGR-A, PGR-B, MMP-2 and MMP-9 mRNA expression was performed using Real-time PCR in ectopic and eutopic tissues. Then, Statistical analysis was calculated according to the 2-ΔΔCT equation for all samples. Results: Quantitative RT–PCR analyses of PGR-A and PGR-B mRNA revealed that there were differences in both isoformes of PGRs mRNA expressions between ectopic and control eutopic tissues. We were able to demonstrate low expression levels of PGR-B isoforms in ectopic tissues. Although, PGR-A expression was significantly higher in the same ectopic samples compare to controls.This method permitted us to demonstrate significant overexpression of MMP-2 and MMP-9 in ectopic samples compared to control endometrial tissues, as well. Conclusions: Our data suggest that low expression levels of PGR-B and overexpression of PGR-A can alter PGR-A/PGR-B ratio in endometriotic ectopic tissues. Imbalance ratio of PGRs in endometriotic tissue may be able to consequence MMP-2 and MMP-9 overexpression which can be important in pathogenesis and treatment of disease.

Keywords: endometriosis, matrix metalloproteinases, progesterone receptor -A and -B, PGR-A/PGR-B ratio

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Authors: Sabrina Barsky, Ashley Monks

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In humans, exercise improves symptoms of various pathological states, although exercise adaptations seem to differ in response to sex. Skeletal muscle anabolism is thought to be regulated by androgen receptor (AR) through poorly specified mechanisms. Interactions of AR and exercise on muscle phenotype remain inconclusive in males, and undetermined in females. We hypothesized that sex differences in exercise adaptations are regulated by the androgenic system and the type of exercise performed. Here we examined interactions between a muscle-specific AR overexpression transgene (HSA-AR) and forced aerobic exercise paradigm on muscle and adipose exercise adaptation in male and female rats. We used dual-energy X-ray absorptiometry (DXA) to examine body composition adaptations post 9-week exercise protocol. We replicated the effects of HSA-AR on body composition, with males only having increased % lean mass and reduced % fat mass (P<0.05). Aerobic exercise improved lean body phenotype significantly, with lesser indices of total and % fat mass (P<0.01) in both sexes. Sex-specific effects of exercise included decreased total body mass (P<0.01) in males and increased lean mass % (P<0.001) in females. Surprisingly, neither AR manipulation nor exercise affected bone parameters in either sex. This varied response in total mass and lean mass according to exercise presents a sexually dimorphic response to exercise. Neither sex showed an interaction between HSA-AR and forced aerobic exercise on body composition. Future work is proposed to examine the effects of exercise type (aerobic versus resistance) and the role of gonadal androgens in sexually dimorphic exercise-mediated mitochondrial adaptations. This work implicates the development of sex-specific exercise therapies.

Keywords: androgen receptor, forced exercise, muscle physiology, sexual dimorphism

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Authors: Dorothy Chyung

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In the psychiatric interview, the mental status exam begins with an assessment of the patient's appearance, noting aspects such as grooming and hygiene. However, it is not well established whether further examination of a patient's attire can provide further useful information. The popular assumption is that those who are mentally unwell will manifest this in unusual clothing. In the moral treatment of the 19th century, proper clothing was also seen as a pivotal therapeutic concern. This project examines assumptions about clothing, both as a reflection of and treatment for psychopathology. The methodology considers the opinions expressed in 19th century art and journals, as well as asylum rules, in comparison to contemporary psychiatric practice and research evidence. Per moral treatment in the 19th century, self-discipline and a proper environment would cure insanity. Madness was evident in the opposite of these ideals—such as ragged or ‘improper’ clothing—and rules about attire delineated the most correct (i.e. sane) ways to dress. These rules applied not only for the patients but also for staff. Despite these ideals, accusations were made that asylums, in fact, dressed patients to look more mentally unwell and further removed patients’ agency. Current practice in psychiatric hospitals retains remnants of moral treatment. Patients are expected to dress ‘appropriately’ while retaining some choice to build self-esteem, with arguments about safety being used to justify the removal of choice. Meanwhile, staff is expected to dress professionally and as role models, based on the assumption that conservative dress is least pathological. Research on this subject is limited, and there is little evidence that discrete psychiatric diagnoses manifest in the particular dress, nor that conservative dress would result in a reduction in pathology. Dressing unusually has become a privilege granted only to those without association with mental illness.

Keywords: fashion, history of psychiatry, medical humanities, mental health treatment

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Authors: Kyosuke Kamada, Christoph Kapeller, Michael Jordan, Mostafa Mohammadpour, Christy Li, Christoph Guger

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Cortico-cortical evoked potentials (CCEP) refer to responses generated by cortical electrical stimulation at distant brain sites. These responses provide insights into the functional networks associated with language or motor functions, and in the context of epilepsy, they can reveal pathological networks. Locating the origin and spread of seizures within the cortex is crucial for pre-surgical planning. This process can be enhanced by employing cortical stimulation at the seizure onset zone (SOZ), leading to the generation of CCEPs in remote brain regions that may be targeted for disconnection. In the case of a 24-year-old male patient suffering from intractable epilepsy, corpus callosotomy was performed as part of the treatment. DTI-MRI imaging, conducted using a 3T MRI scanner for fiber tracking, along with CCEP, is used as part of an assessment for surgical planning. Stimulation of the SOZ, with alternating monophasic pulses of 300µs duration and 15mA current intensity, resulted in CCEPs on the contralateral frontal cortex, reaching a peak amplitude of 206µV with a latency of 31ms, specifically in the left pars triangularis. The related fiber tracts were identified with a two-tensor unscented Kalman filter (UKF) technique, showing transversal fibers through the corpus callosum. The CCEPs were monitored through the progress of the surgery. Notably, the SOZ-associated CCEPs exhibited a reduction following the resection of the anterior portion of the corpus callosum, reaching the identified connecting fibers. This intervention demonstrated a potential strategy for mitigating the impact of intractable epilepsy through targeted disconnection of identified cortical regions.

Keywords: CCEP, SOZ, Corpus callosotomy, DTI

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Authors: Yaya Gao, Jifeng Liu, Yafeng Liu

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Objectives: This study aimed to improve clinicians' understanding and diagnosis of the Mammary analogue secretory carcinoma of the salivary gland（MASC）. Methods: The clinical features of a MASC patient who was admitted to WestChina Hospital of Sichuan University in July 2020 were reviewed and analyzed. A 49-year-old woman with left upper neck pain for three months was admitted to the hospital. She underwent adenoma resection of the left submandibular gland 14 years ago and mucoepidermoid carcinoma resection surgery five years ago. Three months before admission, the patient developed pain in the left mandibular angle after "fatigue" and gradually developed radiation pain in the left ear, which could be relieved after rest. A mass of 1cm could be touched at the mandibular, with tenderness, poor mobility, and hard texture. No swelling, heat, pain, rupture, or pus was found on the surrounding skin. Color doppler ultrasonography of the salivary gland indicated a weak echo mass of 23*14*17mm in the left parotid gland. Results: Surgical excision was completed. Immunohistochemistry of the tumor samples after operation showed that P63（a few，+）, CK7（+）, S100（+）, DOG1（-）, Ki67（MIB-1）（+，5%），pan-TRK（+）, PAS(+) . ETV-6 gene translocation was detected in FISH in postoperative pathology, which indicated MASC. After this diagnosis, the patient sent the postoperative specimen of the second submandibular tumor to our hospital for consultation. The morphology of the two was similar. FISH detected ETV-6 gene translocation, so the second pathological diagnosis was revised to MASC. Conclusion: MASC of the salivary gland is a rare salivary gland tumor whose diagnosis depends on the result of the ETV6-NTRK3 fusion gene.

Keywords: mammary analogue secretory carcinoma, ETV6-NTRK3, salivary gland, misdiagnosed

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Authors: Edward Poluyi, Eghosa Morgan, Charles Poluyi, Chibuikem Ikwuegbuenyi, Grace Imaguezegie

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Background: Current epidemiological studies have examined the associations between moderate and severe traumatic brain injury (TBI) and their risks of developing neurodegenerative diseases. Concussion, also known as mild TBI (mTBI), is however quite distinct from moderate or severe TBIs. Only few studies in this burgeoning area have examined concussion—especially repetitive episodes—and neurodegenerative diseases. Thus, no definite relationship has been established between them. Objectives : This review will discuss the available literature linking concussion and amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease (AD). Materials and Methods: Given the complexity of this subject, a realistic review methodology was selected which includes clarifying the scope and developing a theoretical framework, developing a search strategy, selection and appraisal, data extraction, and synthesis. A detailed literature matrix was set out in order to get relevant and recent findings on this topic. Results: Presently, there is no objective clinical test for the diagnosis of concussion because the features are less obvious on physical examination. Absence of an objective test in diagnosing concussion sometimes leads to skepticism when confirming the presence or absence of concussion. Intriguingly, several possible explanations have been proposed in the pathological mechanisms that lead to the development of some neurodegenerative disorders (such as ALS and AD) and concussion but the two major events are deposition of tau proteins (abnormal microtubule proteins) and neuroinflammation, which ranges from glutamate excitotoxicity pathways and inflammatory pathways (which leads to a rise in the metabolic demands of microglia cells and neurons), to mitochondrial function via the oxidative pathways.

Keywords: amyotrophic lateral sclerosis, Alzheimer's disease, mild traumatic brain injury, neurodegeneration

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Authors: N. Hachemi, I. Benmehdi, O. Hasnaoui

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The air like water is an essential element for living beings. Each day, a man breathes about 20m3 of air. It originally consists of a set of gas whose presence and concentrations correspond to the needs of life. This study focuses on air pollution by smoke and dust emitted from the chimney of the cement works of Beni Saf, pathological and their impact on the environment. Dust of the cement plant are harmless to permissible levels for living organisms, but the two combined phenomena namely the release of dust and aridity of the climate, which severely marked area of Beni Saf; have contributed adverse effects in on human health and the degradation of vegetation cover and species especially weakened by environmental stress. The most visible impact is certainly the deposition of dust on the surrounding areas of the cement factory, and seriously affecting the aesthetics of the landscape. Health problems are more important inside and outside the factory. Among the diseases notable caused by the cement works are: deafness, heart disease, asthma and mental. The dust of the cement works is mainly composed of fine particles of limestone, clay, free lime, silicates and also loaded of the gases such as carbon dioxide gas CO2. The accumulation of this gas in the atmosphere is directly involved in the phenomenon of increasing of greenhouse effect. Some gases, for example, are directly toxic. They can change the climate, changing precipitation types and become a greater source of stress by drought, etc. The environment also suffers from air pollution indirectly; it is more precisely the acid rain. They are produced by the combustion of non-metals in air. Acid rain has consequences for contaminating the soil, weakening the flora, fauna and acidifies lakes. Finally, the pollution problems are multiple and specific dust. It can worsen and change, it has reached epidemic proportions quantitatively and qualitatively disturbing and unpredictable.

Keywords: atmospheric pollution, cement, dust, environment

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Authors: Rachel Shukrun, Szilvia Baron, Victoria Fidel, Anna Shusterman, Osnat Sher, Netanya Kollender, Dror Levin, Yair Peled, Yair Gortzak, Yoav Ben-Shahar, Revital Caspi, Sagi Gordon, Michal Manisterski, Ronit Elhasid

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Ewing sarcoma (EWS) is a highly aggressive cancer with a survival rate of 70–80% for patients with localized disease and under 30% for those with metastatic disease. Tumor-infiltrating neutrophils (TIN) can generate extracellular net-like DNA structures known as neutrophil extracellular traps (NETs). However, little is known about the presence and prognostic significance of tumor-infiltrating NETs in EWS. Herein, we investigated 46 patients diagnosed with EWS and treated in the Tel Aviv Medical Center between 2010 and 2021. TINs and NETs were identified in diagnostic biopsies of EWS by immunofluorescent. In addition, NETs were investigated in neutrophils isolated from peripheral blood samples of EWS patients at diagnosis and following neoadjuvant chemotherapy. The relationships between the presence of TINs and NETs, pathological and clinical features, and outcomes were analyzed. Our results demonstrate that TIN and NETs at diagnosis were higher in EWS patients with metastatic disease compared to those with local disease. High NETs formation at diagnosis predicted poor response to neo-adjuvant chemotherapy, relapse, and death from disease (P < .05). NETs formation in peripheral blood samples at diagnosis was significantly elevated among patients with EWS compared to pediatric controls and decreased significantly following neoadjuvant chemotherapy. In conclusion, NETs formation seems to have a role in the EWS immune microenvironment. Their presence can refine risk stratification, predict chemotherapy resistance and survival, and serve as a therapeutic target in patients with EWS.

Keywords: Ewing sarcoma, tumor microenvironment, neutrophil, neutrophil extracellular traps (NETs), prognosis

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Authors: Jorge Iván Bañol-Betancur, Lina María Martínez-Sánchez, María de los Ángeles Rodríguez-Gázquez, Estefanía Bahamonde-Olaya, Ana María Gutiérrez-Tamayo, Laura Isabel Jaramillo-Jaramillo, Camilo Ruiz-Mejía, Natalia Morales-Quintero

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Acute chest pain is a distressing sensation between the diaphragm and the base of the neck and it represents a diagnostic challenge for any physician in the emergency department. Objective: To establish the main clinical and epidemiological characteristics of patients who present with chest pain to the emergency department in a private clinic from the city of Medellin, during 2014-2015. Methods: Cross-sectional retrospective observational study. Population and sample were patients who consulted for chest pain in the emergency department who met the eligibility criteria. The information was analyzed in SPSS program vr.21; qualitative variables were described through relative frequencies, and the quantitative through mean and standard deviation ‬or medians according to their distribution in the study population. Results: A total of 231 patients were evaluated, the mean age was 49.5 ± 19.9 years, 56.7% were females. The most frequent pathological antecedents were hypertension 35.5%, diabetes 10,8%, dyslipidemia 10.4% and coronary disease 5.2%. Regarding pain features, in 40.3% of the patients the pain began abruptly, in 38.2% it had a precordial location, for 20% of the cases physical activity acted as a trigger, and 60.6% was oppressive. Costochondritis was the most common cause of chest pain among patients with an established etiologic diagnosis, representing the 18.2%. Conclusions: Although the clinical features of pain reported coincide with the clinical presentation of an acute coronary syndrome, the most common cause of chest pain in study population was costochondritis instead, indicating that it is a differential diagnostic in the approach of patients with pain acute chest.

Keywords: acute coronary syndrome, chest pain, epidemiology, osteochondritis

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Authors: Hasan Frookh Jamal

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This is a case of a 36-year-old Bahraini gentleman diagnosed to have Cushing's Syndrome with a large anterior mediastinal mass. He was sent abroad to the Speciality hospital in Jordan, where he underwent diagnostic video-assisted thoracoscopy, partial thymectomy and pericardial fat excision. Histopathology of the mass was reported to be an Atypical carcinoid tumor with a low Ki67 proliferation index of 5%, the mitotic activity of 4 MF/10HPF and pathological stage classification(pTNM): pT1aN1. MRI of the pituitary gland showed an ill-defined non-enhancing focus of about 3mm on the Rt side of the pituitary on coronal images, with a similar but smaller one on the left side, which could be due to enhancing pattern rather than a real lesion as reported. The patient underwent Ga68 Dotate PET/CT scan post-operatively, which showed multiple somatostatin receptor-positive lesions seen within the tail, body and head of the pancreas and positive somatostatin receptor lymph nodes located between the pancreatic head and IVC. There was no uptake detected at the anterior mediastinum nor at the site of thymic mass resection. There was no evidence of any positive somatostatin uptake at the soft tissue or lymph nodes. The patient underwent IPSS, which proved that the source is, in fact, an ectopic source of ACTH secretion. Unfortunately, the patient's serum cortisol remained elevated after surgery and failed to be suppressed by 1 mg ODST and by 2 days LLDST with a high ACTH value. The patient was started on Osilodrostat for treatment of hypercortisolism for the time being and his future treatment plan with Lutetium-177 Dotate therapy vs. bilateral adrenalectomy is to be considered in an MDT meeting.

Keywords: cushing syndrome, neuroendocrine tumur, carcinoid tumor, Thymoma

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Authors: Valeriy M. Kondratev, Ekaterina A. Vyacheslavova, Talgat Shugabaev, Alexander S. Gudovskikh, Alexey D. Bolshakov

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Modern sensorics imposes strict requirements on the biosensors characteristics, especially technological feasibility, and selectivity. There is a growing interest in the analysis of human health biological markers, which indirectly testifying the pathological processes in the body. Such markers are acids and alkalis produced by the human, in particular - ammonia and hydrochloric acid, which are found in human sweat, blood, and urine, as well as in gastric juice. Biosensors based on modern nanomaterials, especially low dimensional, can be used for this markers detection. Most classical adsorption sensors based on metal and silicon oxides are considered non-selective, because they identically change their electrical resistance (or impedance) under the action of adsorption of different target analytes. This work demonstrates a feasible frequency-resistive method of electrical impedance spectroscopy data analysis. The approach allows to obtain of selectivity in adsorption sensors of a resistive type. The method potential is demonstrated with analyzis of impedance spectra of silicon nanowires in the presence of NH3 and HCl vapors with concentrations of about 125 mmol/L (2 ppm) and water vapor. We demonstrate the possibility of unambiguous distinction of the sensory signal from NH3 and HCl adsorption. Moreover, the method is found applicable for analysis of the composition of ammonia and hydrochloric acid vapors mixture without water cross-sensitivity. Presented silicon sensor can be used to find diseases of the gastrointestinal tract by the qualitative and quantitative detection of ammonia and hydrochloric acid content in biological samples. The method of data analysis can be directly translated to other nanomaterials to analyze their applicability in the field of biosensory.

Keywords: electrical impedance spectroscopy, spectroscopy data analysis, selective adsorption sensor, nanotechnology

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Authors: Ximena Calle, Plinio Cantero-López, Felipe Muñoz-Córdova, Mayarling-Francisca Troncoso, Sergio Lavandero, Valentina Parra

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MUL1, a mitochondrial E3 ubiquitin ligase anchored to the outer mitochondrial membrane, is highly expressed in the heart. MUL1 is involved in multiple biological pathways associated with mitochondrial dynamics. Increased MUL1 affects the balance between fission and fusion, affecting mitochondrial function, which plays a crucial role in myocardial function. Therefore, it is interesting to evaluate the effect of cardiac-specific overexpression of MUL1 on myocardial function. Aim: To determine heart functionality in a mouse model with cardio-specific overexpression MUL1 protein. Methods and Results: Male C57BL/Tg transgenic mice with cardiomyocyte-specific overexpression of MUL1 (n=10) and control (n=4) were evaluated at 12, 27, and 35 weeks of age. Glucose tolerance curve determination was performed after a 6-hours fast to assess metabolic capacity, treadmill test, and systolic, and diastolic pressure was evaluated by the mouse tail-cuff blood pressure system equipment. The result showed no glucose tolerance curve, and the treadmill test demonstrated no significant changes between groups. However, substantial changes in diastolic function were observed by ultrasound and determination of cardiac hypertrophy proteins by western blot. Conclusions: Cardio-specific overexpression of MUL1 in mice without any treatment affects diastolic cardiac function, thus showing the important role contributed by MUL1 in the heart. Future research should evaluate the effect of cardiomyocyte-specific overexpression of MUL1 in pathological conditions such as a high-fat diet is one of the main risk factors for cardiovascular disease.

Keywords: diastolic dysfunction, hypertrophy cardiac, mitochondrial E3 ubiquitin ligase 1, MUL1

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Authors: Warda Jabeen, Romaisa Shamim Khan, Osama Shakeel, Ahmed Faraz Bhatti, Raza Hussain

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Background: The worldwide incidence of cutaneous melanoma (CM) has been on the rise over the past few decades. Primary prevention and early treatment remain the focus of management to reduce the burden of disease. This entails identification of risk factors to prompt early diagnosis. In Pakistan, there is a scarcity of clinico-pathological data relating to cutaneous malignant melanoma. Objective: The purpose of this study was to analyze the epidemiological and clinical characteristics of patients presenting with cutaneous malignant melanoma in Pakistan, and to compare the results with other studies. Method: Shaukat Khanum Memorial Cancer Hospital and Research Centre is currently the only dedicated cancer hospital in the country, accepting patients from all over Pakistan. Majority of the patients, however, belong to the northern half of the country. From the recorded data of the hospital, all cutaneous melanoma cases were identified and evaluated. Results: Between 1997 and 2017, a total of 169 cutaneous melanoma patients were registered at Shaukat Khanum. Mean age was 47.5 years. The highest incidence of melanoma was seen in the age group 40-59 years (n=69, 40.8%). Most commonly reported clinical subtype was unspecified melanoma (n=154, 91%). Amongst those in which T stage was reported, the most frequently observed T-stage at presentation was T4 (n=23, 13.6%). With regards to body distribution, in our study CM was seen most commonly in the lower limb including the hip. The yearly incidence of melanoma has increased/remained stable from 2007 to 2017. Conclusion: cutaneous malignant melanoma is a fairly common disease in Pakistan. Patients tend to present at a more advanced stage as compared to patients in developed countries. Identification of risk factors and tumor characteristics is therefore of paramount importance to deal with these patients.

Keywords: epidemiology of cutaneous malignant melanoma, cutaneous malignant melanoma, Pakistan, skin cancer

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Authors: Surender Singh, Yogendra Kumar Gupta

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Boerhaavia diffusa (BD) Linn. belonging to family Nyctaginaceae is a herbaceous plant and known as ‘punarnava’ in Hindi, used as herbal medicine for pain relief and various ailments. It is widely used as a green leafy vegetable in many Asian and African countries. The objective of present study was to investigate potential adverse effects, if any, of standardized root extract of Boerhaavia diffusa in rats following subchronic administration. In acute toxicity study, no mortality was found at a dose of 2000mg/kg which indicates that oral LD50 of Boerhaavia diffusa root extract is more than 2000mg/kg. The chronic administration of Boerhaavia diffusa for 28 days at a dose of 1000mg/kg body weight did not produce any significant changes in hematological (RBC, WBC, platelets, hemoglobin, bleeding time, clotting time) and biochemical (triglycerides, blood glucose, high density lipoprotein, serum creatinine, serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase) parameters of male and female rats as compared to normal control group. All the animals survived until the scheduled necropsy, and their physical and behavioral examinations did not reveal any treatment-related adverse effects. No pathological changes were observed in histological section of heart, kidney, liver, testis, ovaries and brain of Boerhaavia diffusa treated male and female rats as compared to normal control animals.These observations from oral acute toxicitystudy suggest that the extract is practically non-toxic. Thus, it can be inferred that the Boerhaavia diffusa root extract at levels up to 1000 mg/kg/day was found to be safe and does not cause adverse effects in rats. So, the no-observed effect level (NOAEL) of the extract was found to be 1000mg/kg/day.

Keywords: Boerhaavia diffusa, histology, toxicity, sub-acute

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Authors: Bindu I. Somarajan, Viney Gupta, Gagandeep Kaur Walia, Jasbir Kaur, Sunil Kumar, Shikha Gupta, Abadh K. Chaurasia, Dinesh Gupa, Abhinav Kaushik, Aditi Mehta, Vipin Gupta, Arundhati Sharma

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Background: Juvenile onset primary open angle glaucoma (JOAG), affects individuals under the age of 40 years. Studies on a few families of JOAG, that led to the discovery of the Myocilin gene, reported the disease to have an autosomal dominant pattern of inheritance. However, sporadic forms of JOAG been seen to be more common in some populations. Most pathological homozygous mutations in the CYP1B1 gene associated with JOAG have been seen among sporadic cases. Given the higher prevalence of sporadic JOAG cases in our population, we aimed to look for common mutations E229K and R368H, the two most common variants in the CYP1B1 gene associated with glaucoma. Objective: To determine the frequency and evaluate genotype phenotype correlation of CYP1B1 E229K and R368H mutations in a cohort of 120 sporadic Juvenile open angle glaucoma patients.Methods: Unrelated JOAG patients whose first degree relatives had been examined and found to be unaffected were included in the study. The patients and their parents were screened for E229K and R368H mutations. The phenotypic characteristics were compared between probands with and with out these mutations by SPSS v16. Results: Out of 120 JOAG patients included in the study, the E229K mutation was seen in 9 probands (7.5%) and R368H in 7 (5.8%). The average age of onset of the disease (p=0.3) and the highest untreated IOP (p=0.4) among those carrying mutations was not significantly different from those who did not have these mutations. The proportion of probands with angle dysgenesis among those with E229K and R368H mutations was 70% (11 out of 16) in comparison to 65% (67 out of 104) of those who did not harbour these mutations (p=0.56). Similarly the probands with moderate to high myopia among those with E229K and R368H mutations was 20% (3 out of 16) in comparison to 18% (18 out of 104) of those who did not harbour these mutations(p=0.59). Conclusion: The frequency of E229K and R368H mutations of the CYP1B1 gene is low even among sporadic JOAG patients. Moreover there is no clinical correlation between the presence of these mutations and disease severity

Keywords: CYP1B1, gene, IOP, JOAG, mutation

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Authors: Liliana Rytel, Jarosław Całka

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One of the diseases that are very common health problem of modern man is the stomach hyperacidity. It is well known that this pathological state, during which gastric glands secrete too much of hydrochloric acid can be caused due to various factors such as stress, eating habits, alcohol, smoking and some, especially anti-inflammatory drugs. Moreover, hyperacidity is recognized as one of factors leading to development of peptic ulcer disease. Therefore, we analyzed expression of substance P (SP) and neuronal isoform of nitric oxide synthase (nNOS) in the porcine nodose ganglion sensory neurons innervating prepyloric stomach region in physiological state and following intragastric infusion of hydrochloric acid. The study was performed on 8 immature gilts of the Large White Polish breed. All animals were injected retrograde marker Fast Blue (FB) into the anterior prepyloric stomach wall. After injections of FB, pigs were divided into two groups: control (group C; n = 4) and experimental (HCL group, n = 4) and after convalescence period of 23 days, animals of HCL group were subjected to renewed anaesthesia. Then, 0.25 M aqueous solution of hydrochloric acid with a dose of 5 ml/kg body weight was administered intragastrically with use of a stomach tube. On 28th day, all control and HCL pigs were euthanized and bilateral reght (rNG) and left (lNG) were collected. Cryostat sections were processed for double immunofluorescence using anibodies against SP and NOS. Immunofluorescence staining in the even-numbered ganglia nodes showed the presence of FB-positive cells expressing SP (45,9 ± 3,38% in rNG and 60,4 ± 1,71% in lNG), and nNOS (34,9 ± 6,83% in rNG and 49,9 ± 9,32% in lNG). In HCL group increased expression of both SP (54,8 ± 5,34% in rNG and 56,9 ± 3,28 % in lNG) as well as nNOS (54,9 ± 4,45% in rNG and 52,5 ± 2,17 % in lNG) in FB+ perikaria was found. The acquired results suggest that SP and nNOS are neurotransmitters and/ or neuromodulators participating in the sensory regulation of the prepyloric region of porcine stomach function as well as their potential role in development of the stomach inflamatory state.

Keywords: nNOS, nodose ganglion, pig, SP

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Authors: Eni Rahmi, Rasmi Rikmasari, Taufik Soemarsongko

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Background: One of the bad habits that requires a treatment and viewed as a risk factor of the temporomandibular disorder is bruxism. Bruxism defined as an awake and/or asleep parafunctional activities include grinding, gnashing, bracing or clenching of the teeth. In particular circumstances such as an increased frequency of episode, duration and the intensity of masseter contractions, caused phenomenon with pathological consequences, i.e., mandibular remodeling. The remodeling in mandibular angle was associated with the masseter and pterygoid medial muscles attachment which in its insertion area. The aim of this study was to compare the mandibular remodeling between bruxers and non-bruxers with ramus height, gonial angle and bigonial width as parameters, and to identify correlation among those parameters in bruxers, using panoramic radiographic. Methods: This study was conducted on 35 bruxers (10 phasic bruxism patients, 6 tonic bruxism patients, and 19 mixed bruxism patients) and 20 non-bruxers as control group. The data were obtained by using questionary, clinical examination, and radiographic measurement. Panoramic radiograph measurement was done using soft CBCT EPX Impla (E-Woo Korea). The data was analyzed by using Paired T-Test to see differences between parameters in both group and Pearson Correlation Test to evaluate correlation among parameters. Result: There was significant differences between bruxers and non-bruxers in ramus heights (p=0,04), bigonial widths (p=0,001), and gonial angles(p=0,015). The bruxers showed increased ramus heights and bigonial widths, in other hand, the gonial angles decreased. This study also found that there was highly correlation among ramus height, gonial angles, and bigonial widths. Conclusion: the bone remodeling occurred on inferior and posterior border of mandibular angle in bruxism patient, indicated by the form and size differences between bruxers (phasic bruxism, tonic bruxism, and mixed bruxism) with non-bruxers, which shown by panoramic radiograph.

Keywords: bruxism, ramus height, gonial angle, bigonial width

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Authors: Saad Al-Shibli, Nasser Amjad, Muna Al Kubaisi, Norra Harun, Shaikh Mizan

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Leptin is a multifunctional hormone produced mainly by adipocyte. Leptin and its receptor have long been found associated with breast cancer. The main aim of this study is to investigate the correlation between Leptin/Leptin receptor and the clinicopathological features of breast cancer. Blood samples for ELISA, tissue samples from tumors and adjacent breast tissue were taken from 51 women with breast cancer with a control group of 40 women with a negative mammogram. Leptin and Leptin receptor in the tissues were estimated by immunohistochemistry (IHC). They were localized at the subcellular level by immunocytochemistry using transmission electron microscopy (TEM). Our results showed significant difference in serum leptin level between control and the patient group, but no difference between pre and post-operative serum leptin levels in the patient group. By IHC, we found that the majority of the breast cancer cells studied, stained positively for leptin and leptin receptors with co-expression of leptin and its receptors. No significant correlation was found between leptin/leptin receptors expression with the race, menopausal status, lymph node metastasis, estrogen receptor expression, progesterone receptor expression, HER2 expression and tumor size. Majority of the patients with distant metastasis were associated with high leptin and leptin receptor expression. TEM views both Leptin and Leptin receptor were found highly concentrated within and around the nucleus of the cancer breast cells, indicating nucleus is their principal seat of actions while the adjacent breast epithelial cells showed that leptin gold particles are scattered all over the cell with much less than that of the cancerous cells. However, presence of high concentration of leptin does not necessarily prove its over-expression, because it could be internalized from outside by leptin receptor in the cells. In contrast, leptin receptor is definitely over-expressed in the ductal breast cancer cells. We conclude that reducing leptin levels, blocking its downstream tissue specific signal transduction, and/or blocking the upstream leptin receptor pathway might help in prevention and therapy of breast cancer.

Keywords: breast cancer, expression, leptin, leptin receptors

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Authors: M. Reza Roshandel, Tannaz Aghaei Badr, Batoul Khoundabi, Sara C. Lewis, Soroush Rais-Bahrami, John Sfakianos, Reza Mehrazin, Ash K. Tewari

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Introduction: Prostate biopsy is the most reliable diagnostic method for choosing the appropriate management of prostate cancer. However, discrepancies between Gleason grade groups (GG) of different biopsies remain a significant concern. This study aims to assess the association of the radiological factors with GG discrepancies in patients with index Prostate Imaging Reporting and Data System (PI-RADS) 3 lesions, using radical prostatectomy (RP) specimens as the most accurate and informative pathology. Methods: This single-institutional retrospective study was performed on a total of 2289 consecutive prostate cancer patients with combined targeted and systematic prostate biopsy followed by radical prostatectomy (RP). The database was explored for patients with the index PI-RADS 3 lesions version 2 and 2.1. Cancers with PI-RADS 4 or 5 scoring were excluded from the study. Patient characteristics and radiologic features were analyzed by multivariable logistic regression. Number-density of lesions was defined as the number of lesions per prostatic volume. Results: Of the 151 prostate cancer cases with PI-RADS 3 index lesions, 27% and 17% had upgrades and downgrades at RP, respectively. Analysis of grade changes showed no significant associations between discrepancies and the number or the number density of PI-RADS 3 lesions. Moreover, the study showed no significant association of the GG changes with race, age, location of the lesions, or prostate volume. Conclusions: This study demonstrated that in PI-RADS 3 cancerous nodules, the chance of the pathology changes in the final pathology of RP specimens was low. Furthermore, having multiple PI-RADS 3 nodules did not change the conclusion, as the possibility of grade changes in patients with multiple nodules was similar to those with solitary lesions.

Keywords: prostate, adenocarcinoma, multiparametric MRI, Gleason score, robot-assisted surgery

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Authors: Titis Indah Adi Rahayu

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Angiogenesis is the process of generating new capillary from pre-existing blood vessels. VEGFA is a major regulator in angiogenesis that binds and activates two tyrosine kinase receptors, VEGFR1 (Flt-1) and VEGFR2 (Flk-1/KDR) which regulate pathological and physiological angiogenesis. Disruption of VEGFA and VEGFR2 regulation lead to many diseases. The study of α-Mangostin (derivate of xanthone) as anti-oxidant and anti inflammation has been explored recently and both of them have relation to vasculature however the effect of α-Mangostin in blood vessel formation in healthy tissue in vivo has not been studied. Zebrafish is a powerful model in studying angiogenesis and shared many advantages that is a viable whole animal model for screening small molecules that affect blood vessel formation. Therefore the aim of this study is to evaluate angiogenic activity of α-Mangostin in healthy tissue in vivo in zebrafish embryo in relation of patterning blood vessel. Blood vessel patterning is highly characteristic in the developing of zebrafish embryo and the subintestinal vessel (SIV) can be stained and visualized microscopically as a primary screen for α-Mangostin that effect angiogenesis. The zebrafish embryos are divided into 2 groups. Group one consists of the zebrafish embryos at 1 dpf for 4 days which are tested to α-Mangostin in several concentration 2 µM, 4 µM, 6 µM, 8 µM and 10 µM whereas in group two the zebrafish larva at 4 dpf are exposed to α-Mangostin 1,75 µM, 2,3 µM, 2,9 µM, 3,8 µM dan 5 µM for 2 days. DMSO is served as a control for each group. The level expression of vegfa and vegfr2 are observed quantitatively using real time q-PCR and patterning of SIV are then analized via alkaline phospatase staining. Result shows that the level expression of vegfa and vegfr2 is repressed quantitatively as shown in real time q-PCR in the group of 1-4 days of α-Mangostin exposure where it is increased in the group of 4-6 days of α-Mangostin exposure. The result is then compared to alkaline phospatase staining of SIV using stereo microscope. It indicates that α-Mangostin does not disturb the patterning of SIV formation in zebrafish.

Keywords: angiogenesis, Danio rerio, α-Mangostin, SIV, vegfa, vegfr2

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Authors: Muner M. B. Mohamed, Vipin Varghese, Dustin Chalmers, Khalid M. G. Mohammed, Juan Carlos Q. Velez

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Background: Urinary waxy casts (uWxC) are traditionally described in textbooks as indicative of chronic renal parenchymal disease. However, data supporting this contention is lacking. uWxC can be seen in the context of various renal syndromes, including acute kidney injury, chronic kidney disease, rapidly progressive glomerulonephritis (GN), and nephrotic syndrome. Thus, we investigated the correlation between the identification of uWxC and renal pathological findings. Methods: We prospectively collected data of patients seen in nephrology consultation with a urine specimen subjected to the microscopic examination of the urinary sediment (MicrExUrSed) over a 3-year period. Within this cohort, we identified cases in which a kidney biopsy was concomitantly performed. We assessed the association of uWxC with glomerular or tubular pathology and with chronicity [interstitial fibrosis and tubular atrophy (IFTA) and glomerular obsolescence (GO)]. Results: Among 683 patients with MicrExUrSed,103 (15%) underwent kidney biopsy and were included. The mean age was 55 years, 51% women, 50% white, and 38% self-identified black. Median serum creatinine was 3.2 (0-7-15.6) mg/dL and not significantly different between those with and without uWxC (4.7 vs 3.8 mg/dL, p=0.13). uWxC was identified in 35 (34%) cases. A glomerulopathy was diagnosed in 79 (77%). Among those with uWxC (n=35), a glomerulopathy was more likely to be found with concomitant acute tubular injury (ATI) than without ATI (57% vs. 23%, p=0.0006), whereas among those without uWxC, glomerulopathies were found with or without concomitant ATI with similar frequency (41% vs. 34%, p=0.48). Overall (n=103), more patients with uWxC had ≥ 20% IFTA compared to those without uWxC (74% vs 51%, p=0.03). Among those with glomerulopathy (n=79), more patients with uWxC had ≥ 20% IFTA compared to those without uWxC (89% vs. 56%, p=0.004). uWxC did not correlate with GO. Conclusion: Identification of uWxC denotes a greater likelihood of finding evidence of ATI superimposed with a glomerulopathy rather than finding an isolated glomerular lesion. uWxC is associated with a greater probability of finding ≥ 20% IFTA in a kidney biopsy specimen, particularly in those with a glomerular pathology. This observation may help clinicians weigh on the suitability of a kidney biopsy when chronicity or coexistence of ATI is in question.

Keywords: waxy cast, kidney biopsy, acute tubular injury, glomerulopathy

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Authors: Radka Gorejova, Ivana Sisolakova, Jana Shepa, Frederika Chovancova, Renata Orinakova

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Diabetes mellitus (DM) is a serious metabolic disease characterized by chronic hyperglycemia. Often, the symptoms are not sufficiently observable at early stages, and so hyperglycemia causes pathological and functional changes before the diagnosis of the DM. Therefore, the development of an electrochemical sensor that will be fast, accurate, and instrumentally undemanding is currently needful. Screen-printed carbon electrodes (SPCEs) can be considered as the most suitable matrix material for insulin sensors because of the small size of the working electrode. It leads to the analyst's volume reduction to only 50 µl for each measurement. The surface of bare SPCE was modified by a combination of chitosan, multi-walled carbon nanotubes (MWCNTs), and zinc nanoparticles (ZnNPs) to obtain better electrocatalytic activity towards insulin oxidation. ZnNPs were electrochemically deposited on the chitosan-MWCNTs/SPCE surface using the pulse deposition method. Thereafter, insulin was determined on the prepared electrode using chronoamperometry and electrochemical impedance spectroscopy (EIS). The chronoamperometric measurement was performed by adding a constant amount of insulin in 0.1 M NaOH and PBS (2 μl) with the concentration of 2 μM, and the current response of the system was monitored after a gradual increase in concentration. Subsequently, the limit of detection (LOD) of the prepared electrode was determined via the Randles-Ševčík equation. The LOD was 0.47 µM. Prepared electrodes were studied also as the impedimetric sensors for insulin determination. Therefore, various insulin concentrations were determined via EIS. Based on the performed measurements, the ZnNPs/chitosan-MWCNTs/SPCE can be considered as a potential candidate for novel electrochemical sensor for insulin determination. Acknowledgments: This work has been supported by the projects Visegradfund project number 22020140, VEGA 1/0095/21 of the Slovak Scientific Grant Agency, and APVV-PP-COVID-20-0036 of the Slovak Research and Development Agency.

Keywords: zinc nanoparticles, insulin, chronoamperometry, electrochemical impedance spectroscopy

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Authors: Ammara Khan

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Sepsis is characterized by an overwhelming surge of cytokines and oxidative stress to one of many factors, gram-negative bacteria commonly implicated. Despite major expansion and elaboration of sepsis pathophysiology and therapeutic approach; death rate remains very high in septic patients due to multiple organ damages including hepatotoxicity.The present study was aimed to ascertain the adequacy of three different drugs delivered separately and collectively- low dose steroid-dexamethasone (3mg/kg i.p) ,antioxidant-melatonin(10 mg/kg i.p) ,and phosphodiesterases inhibitor - pentoxifylline (75 mg/kg i.p)in endotoxin-induced hepatotoxicity in mice. Endotoxin/lipopolysaccharides induced hepatotoxicity was reproduced in mice by giving lipopolysaccharide of serotype E.Coli intraperitoneally. The preventive role was questioned by giving the experimental agent half an hour prior to LPS injection whereas the therapeutic potential of the experimental agent was searched out via post-LPS delivering. The extent of liver damage was adjudged via serum alanine aminotransferases (ALT) and aspartate aminotransferase (AST) estimation along with a histopathological examination of liver tissue. Dexamethasone is given before (Group 3) and after LPS (group 4) significantly attenuated LPS generated liver injury.Pentoxifylline generated similar results and serum ALT; AST histological alteration abated considerably (p≤ 0.05) both in animals subjected to pentoxifylline pre (Group 5) and post-treatment(Group 6). Melatonin was also prosperous in aversion (Group 7) and curation (Group 8) of LPS invoked hepatotoxicity as evident by lessening of augmented ALT (≤0.01) and AST (≤0.01) along with restoration of pathological changes in liver sections (p≤0.05). Combination therapies with dexamethasone in conjunction with melatonin (Group 9), dexamethasone together with pentoxifylline (Group 10), and pentoxifylline along with melatonin (Group 11) after LPS administration tapered LPS evoked hepatic dysfunction statistically considerably. In conclusion, both melatonin and pentoxifylline set up promising results in endotoxin-induced hepatotoxicity and can be used therapeutic adjuncts to conventional treatment strategies in sepsis-induced liver failure.

Keywords: endotoxin/lipopolysacchride, dexamethasone, hepatotoxicity, melatonin, pentoxifylline

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Authors: A. D. Paryuni, R. N. Nataria, R. Wasito

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Layer chickens are a poultry commodity that has an important role in producing eggs and meat to support the availability of animal proteins. The layer chickens still have obstacles to increasing their productivity, especially due to poultry diseases which can result not only in decreased egg production but also morbidity and mortality. To overcome this condition, phyto-therapeutic and/or phyto-preventive approaches which are efficacious, safe and cheap are needed. One of the herbal spices from Indonesia which is greatly possible to be promoted as an herbal medicine is a red onion (Allium cepa). The objective of the present study was to identify and determine the effect of red onion extract (Allium cepa) as anti-infection and immuno-modulator of Bursa fabricius in layer chickens raised in an open house system. Eighteen layer chickens at 17 days of age were divided randomly into three group of six each. Those were layer chickens without red onion extract (Group K I), Group K II gave red onion extract via drinking water and Group K III gave red onion extract peroral for 30 days. Water and feed were given ad libitum. Necropsy was conducted every 10 days by taking two samples of layer chickens/Group. Bursa fabricius was processed histopathologically and stained-routinely with hematoxylin-eosinand was then examined under light microscope. The results of the present study indicated that bursaFabricius in layer chickens in Groups K I, K II, and K III that were necropsied at days 10 and 20 had normal histologic structures. However, Bursa fabricius in Group K I at day 30, had vacuolization with mild to moderate large vacuoles containing homogenous eosinophilic fluid and atrophy of lymphoid follicles. Mild vacuolization in the follicle of Bursa fabricius was seen in layer chickens in Group K II, whereas layer chickens in Group K III had normal histologic structures of Bursa fabricius. It was concluded that apparently, red onion extract (Allium cepa) has herbal preventive effects against the pathological lesions in the Bursa fabricius of layer chickens.

Keywords: Bursa fabricius, disease of poultry, hematoxylin-eosin, layer chickens, red onion extract

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Authors: Dona Pamoda W. Jayatunga, Veer Bala Gupta, Eugene Hone, Ralph N. Martins

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Being a neurodegenerative disorder, Alzheimer’s disease (AD) affects a majority of the elderly demented worldwide. The key risk factors for AD are age, metabolic syndrome, allele status of APOE gene, head injuries and lifestyle. The progressive nature of AD is characterized by symptoms of multiple cognitive deficits exacerbated over time, leading to death within a decade from clinical diagnosis. However, it is revealed that AD originates via a prodromal phase that spans from one to few decades before symptoms first manifest. The key pathological hallmarks of AD brains are deposition of amyloid beta (Aβ) plaques and neurofibrillary tangles (NFT). However, the yet unknown etiology of the disease fails to distinguish mitochondrial dysfunction between a cause or an outcome. The absence of early diagnosis tools and definite therapies for AD have permitted recruits of nutraceutical-based approaches aimed at reducing the risk of AD by modulating lifestyle or be used as preventive tools during AD prodromal state before widespread neurodegeneration begins. The objective of the present study was to investigate beneficial effects of luteolin, a plant-based flavone compound, against AD. The neuroprotective effects of luteolin on amyloid beta (Aβ) (1-42)-induced neurotoxicity was measured using cultured human neuroblastoma BE(2)-M17 cells. After exposure to 20μM Aβ (1-42) for 48 h, the neuroblastoma cells exhibited marked apoptotic death. Co-treatment of 20μM Aβ (1-42) with luteolin (0.5-5μM) significantly protected the cells against Aβ (1-42)-induced toxicity, as assessed by the MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2(4sulfophenyl)-2H-tetrazolium, inner salt; MTS] reduction assay and the lactate dehydrogenase (LDH) cell death assay. The results suggest that luteolin prevents Aβ (1-42)-induced apoptotic neuronal death. However, further studies are underway to determine its protective mechanisms in AD including the activity against tau hyperphosphorylation and mitochondrial dysfunction.

Keywords: Aβ (1-42)-induced toxicity, Alzheimer’s disease, luteolin, neuroblastoma cells

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Authors: Maiko Kiyohara, Toshiki Ito

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In this study, we used a psychotherapy process for patient with dissociative disorder and the graphic Rorschach (Digital version) (GRD). A dissociative disorder is a type of dissociation characterized by multiple alternating personalities (also called alternate identity or another identity). "dissociation" is a state in which consciousness, memory, thinking, emotion, perception, behavior, body image, and so on are divided and experienced. Dissociation symptoms, such as lack of memory, are seen, and the repetition of blanks in daily events causes serious problems in life. Although the pathological mechanism of dissociation has not yet been fully elucidated, it is said that it is caused by childhood abuse or shocking trauma. In case of Japan, no reliable data has been reported on the number of patients and prevalence of dissociative disorders, no drug is compatible with dissociation symptoms, and no clear treatment has been established. GRD is a method that the author revised in 2017 to a Graphic Rorschach, which is a special technique for subjects to draw language responses when enforce Rorschach. GRD reduces the burden on both the subject and the examiner, reduces the complexity of organizing data, improves the simplicity of organizing data, and improves the accuracy of interpretation by introducing a tablet computer during the drawing reaction. We are conducting research for the purpose. The patient in this case is a woman in her 50s, and has multiple personalities since childhood. At present, there are about 10 personalities whose main personality is just grasped. The patients is raising her junior high school sons as single parent, but personal changes often occur at home, which makes the home environment inferior and economically oppressive, and has severely hindered daily life. In psychotherapy, while a personality different from the main personality has appeared, I have also conducted psychotherapy with her son. In this case, the psychotherapy process and the GRD were performed to understand the personality characteristics, and the possibility of therapeutic significance to personality integration is reported.

Keywords: GRD, dissociative disorder, a case study of psychotherapy process, dissociation

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Authors: Yu-Wen Cheng, Jau-Der Ho, Liang-Huan Wu, Fan-Li Lin, Li-Huei Chen, Hung-Ming Chang, Yueh-Hsiung Kuo, George Hsiao

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Retina glial activation and neuroinflammation have been confirmed to cause devastating responses in retinodegenerative diseases. The expression and activation of matrix metalloproteinase (MMP)-9 and inducible nitric oxide synthase (iNOS) could be exerted as the crucial pathological factors in glaucoma- and blue light-induced retinal injuries. The present study aimed to investigate the retinoprotective effects and mechanisms of fungal ingredient 3,4-dihydroxybenzalacetone (DBL) isolated from Phellinus linteus in the retinal glial activation and retinodegenerative animal models. According to the cellular studies, DBL significantly and concentration-dependently abrogated MMP-9 activation and expression in TNFα-stimulated retinal Müller (rMC-1) cells. We found the inhibitory activities of DBL were strongly through the STAT- and ERK-dependent pathways. Furthermore, DBL dramatically attenuated MMP-9 activation in the stimulated Müller cells exposed to conditioned media from LPS-stimulated microglia BV-2 cells. On the other hand, DBL strongly suppressed LPS-induced production of NO and ROS and expression of iNOS in microglia BV-2 cells. Consistently, the phosphorylation of STAT was substantially blocked by DBL in LPS-stimulated microglia BV-2 cells. In the evaluation of retinoprotective functions, the high IOP-induced scotopic electroretinographic (ERG) deficit and blue light-induced abnormal pupillary light response (PLR) were assessed. The deficit scotopic ERG responses markedly recovered by DBL in a rat model of glaucoma-like ischemia/reperfusion (I/R)-injury. DBL also reduced the aqueous gelatinolytic activity and retinal MMP-9 expression in high IOP-injured conditions. Additionally, DBL could restore the abnormal PLR and reduce retinal MMP-9 activation. In summary, DBL could ameliorate retinal neuroinflammation and MMP-9 activation by predominantly inhibiting STAT3 activation in the retinal Müller cells and microglia, which exhibits therapeutic potential for glaucoma and other retinal degenerative diseases.

Keywords: glaucoma, blue light, DBL, retinal Müller cell, MMP-9, STAT, Microglia, iNOS, ERG, PLR

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