Search results for: granuloma

Authors: Shreya Ghosh, Akansha Garg, Chayanika Kala, Ashwani Kumar Thakur

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Background: Granuloma formation is one of the characteristic features of tuberculosis. Besides, chronic inflammation underlying tuberculosis is often indicated by an increase in the concentration of serum amyloid A (SAA) protein. The connection between tuberculosis and SAA-driven secondary amyloidosis is well documented. However, SAA-derived amyloid deposition start sites are not well understood in tuberculosis and other chronic inflammatory conditions. It was hypothesized that granuloma could be a potential site for an amyloid deposition because both SAA protein and proteases that cleave SAA into aggregation-prone fragments are reported to be present in the granuloma. Here the authors have shown the presence of SAA-derived amyloid deposits in the granuloma of tuberculosis patients. Methodology: Over a period of two years, tuberculosis patients were screened, and biopsies were collected from the affected organs of the patients. The gold standard, Congo red dye staining, was used to identify amyloid deposits in the tissue sections of tuberculosis patients containing granulomatous structure. Results: 11 out of 150 FFPE biopsy specimens of tuberculosis patients showed eosinophilic hyaline-rich deposits surrounding granuloma. Upon Congo red staining, these deposits exhibited characteristic apple-green birefringence under polarized light, confirming amyloid deposits. Further, upon immunohistochemical staining with anti-SAA, the amyloid enriched areas showed positive immunoreactivity. Conclusion: In this pilot study, we have shown that granuloma can be a potential site for serum amyloid A-derived amyloid formation in tuberculosis patients. Moreover, the presence of amyloid gave significant cues that granuloma might be a probable amyloid deposition start in tuberculosis patients. This study will set a stage to expand the clinical and fundamental research in the understanding of amyloid formation in granuloma underlying tuberculosis and chronic inflammatory conditions.

Keywords: amyloid, granuloma, periphery, serum amyloid A, tuberculosis

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Authors: Richa Sharma, Uma Nahar, Sadhna Sharma, Indu Verma

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Counteracting the deadly pathogen Mycobacterium tuberculosis (M. tb) effectively is still a global challenge. Scrutinizing alternative weapons like antimicrobial peptides to strengthen existing tuberculosis artillery is urgently required. Considering the antimycobacterial potential of Human Beta Defensin 1 (HBD-1) along with isoniazid, the present study was designed to explore the ability of HBD-1 to act against active and dormant M. tb. HBD-1 was screened in silico using antimicrobial peptide prediction servers to identify its short antimicrobial motif. The activity of both HBD-1 and its selected motif (Pep B) was determined at different concentrations against actively growing M. tb in vitro and ex vivo in monocyte derived macrophages (MDMs). Log phase M. tb was grown along with HBD-1 and Pep B for 7 days. M. tb infected MDMs were treated with HBD-1 and Pep B for 72 hours. Thereafter, colony forming unit (CFU) enumeration was performed to determine activity of both peptides against actively growing in vitro and intracellular M. tb. The dormant M. tb models were prepared by following two approaches and treated with different concentrations of HBD-1 and Pep B. Firstly, 20-22 days old M. tbH37Rv was grown in potassium deficient Sauton media for 35 days. The presence of dormant bacilli was confirmed by Nile red staining. Dormant bacilli were further treated with rifampicin, isoniazid, HBD-1 and its motif for 7 days. The effect of both peptides on latent bacilli was assessed by colony forming units (CFU) and most probable number (MPN) enumeration. Secondly, human PBMC granuloma model was prepared by infecting PBMCs seeded on collagen matrix with M. tb(MOI 0.1) for 10 days. Histopathology was done to confirm granuloma formation. The granuloma thus formed was incubated for 72 hours with rifampicin, HBD-1 and Pep B individually. Difference in bacillary load was determined by CFU enumeration. The minimum inhibitory concentrations of HBD-1 and Pep B restricting growth of mycobacteria in vitro were 2μg/ml and 20μg/ml respectively. The intracellular mycobacterial load was reduced significantly by HBD-1 and Pep B at 1μg/ml and 5μg/ml respectively. Nile red positive bacterial population, high MPN/ low CFU count and tolerance to isoniazid, confirmed the formation of potassium deficienybaseddormancy model. HBD-1 (8μg/ml) showed 96% and 99% killing and Pep B (40μg/ml) lowered dormant bacillary load by 68.89% and 92.49% based on CFU and MPN enumeration respectively. Further, H&E stained aggregates of macrophages and lymphocytes, acid fast bacilli surrounded by cellular aggregates and rifampicin resistance, indicated the formation of human granuloma dormancy model. HBD-1 (8μg/ml) led to 81.3% reduction in CFU whereas its motif Pep B (40μg/ml) showed only 54.66% decrease in bacterial load inside granuloma. Thus, the present study indicated that HBD-1 and its motif are effective antimicrobial players against both actively growing and dormant M. tb. They should be further explored to tap their potential to design a powerful weapon for combating tuberculosis.

Keywords: antimicrobial peptides, dormant, human beta defensin 1, tuberculosis

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Authors: Seyyed Mohammad Amin Mousavi Sagharchi, Elham Javanroudi

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Introduction: Tuberculosis (TB) is a known disease with hidden features caused by Mycobacterium tuberculosis (MTB). This disease, which is one of the 10 deadliest in the world, has caused millions of deaths in recent decades. Furthermore, TB is responsible for infecting about 30% population of world. Like any infection, TB can activate the immune system by locating and colonization in the human body, especially in the alveoli. TB is granulomatosis, so MTB can absorb the host’s immune cells and other cells to form granuloma. Method: Different databases (e.g., PubMed) were recruited to prepare this paper and fulfill our goals to search and find effective papers and investigations. Results: Immune response to MTB is related to T cell killers and contains CD1, CD4, and CD8 T lymphocytes. CD1 lymphocytes can recognize glycolipids, which highly exist in the Mycobacterial fatty cell wall. CD4 lymphocytes and macrophages form granuloma, and it is the main line of immune response to Mycobacteria. On the other hand, CD8 cells have cytolytic function for directly killing MTB by secretion of granulysin. Other functions and secretion to the deal are interleukin-12 (IL-12) by induction of expression interferon-γ (INF-γ) for macrophages activation and creating a granuloma, and tumor necrosis factor (TNF) by promoting macrophage phagolysosomal fusion. Conclusion: Immune cells in battle with MTB are macrophages, dendritic cells (DCs), neutrophils, and natural killer (NK) cells. These immune cells can recognize the Mycobacterium by various receptors, including Toll-like receptors (TLRs), Nod-like receptors (NLRs), and C-type lectin receptors (CLRs) located in the cell surface. In human alveoli exist about 50 dendritic macrophages, which have close communication with other immune cells in the circulating system and epithelial cells to deal with Mycobacteria. Against immune cells, MTB handles some factors (e.g., cordfactor, O-Ag, lipoarabinomannan, sulfatides, and adenylate cyclase) and practical functions (e.g., inhibition of macrophages).

Keywords: mycobacterium tuberculosis, immune responses, immunological mechanisms, respiratory tuberculosis

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Authors: Girum Tedla Assefa

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Background: Granulomatous mycosis fungoides is an extremely rare type of cutaneous T-cell lymphoma (<55 cases reported worldwide). Case report: A 36-year-old female presented with soft tissue atrophy of right lower limb (dermis + hypodermis) of 22 years and plaques over trunk of 3 years duration. Histological examination of a biopsy taken from the atrophied tissue showed a granulomatous reaction with epidermotropic atypical lymphocytes. However, in other areas there were only findings of conventional MF without granuloma. Conclusion: The diagnosis of a granulomatous mycosis fungoides depends exclusively on the histological demonstration of granulomas. Distinct clinical characteristics are not present. This case highlights the importance of thorough investigation of lipoatrophic skin changes in the adult to exclude underlying causes, including MF.

Keywords: cutaneous lymphoma, granulomatous skin lymphoma, mycoses fungoides, skin atrophy

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Authors: Ssembatya Joseph Mary

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Introduction: Cryptococcal infection in the Central Nervous System (CNS) is frequently seen in human immunodeficiency virus (HIV) patients and others with low immunity as an opportunistic fungal infection. However, CNS cryptococcal granuloma (cryptococcoma) in immunocompetent patients is rare. We present a case of CNS cryptococcoma in an immunocompetent patient and review the literature to illustrate the diagnosis and treatment of such lesions. Case presentation: A 62-year-old, HIV-negative, immunocompetent female patient with no known chronic illness presented with 5 months history of a progressive headache associated with on and off episodic generalized tonic-clonic convulsions. She had been to several hospitals before she was referred to our center with a diagnosis of a brain tumor. Before referral and despite a negative CSF analysis result, she had received treatment for bacterial meningitis with no success. At Mbarara Regional Referral Hospital (MRRH), she had surgery with an excision biopsy which showed features consistent with cryptococcosis on histology. The patient had a successful adjuvant treatment with antifungal drugs following surgery. Conclusion: The diagnosis of a parasitic CNS infection, particularly cryptococcal infection mimicking neoplastic lesions in an immunocompetent patient, was unusual. Surgical management of such lesions from different reports has a bad outcome and management remains totally conservative.

Keywords: Cryptococcal meningitis, immunocompetent patient, Uganda, low resource setting

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Authors: R. Reshma srilakshmi, S. Shalini, P. Yogeeswari, D. Sriram

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Lysine aminotransferase is a crucial enzyme for dormancy in M. tuberculosis. It is involved in persistence and antibiotic resistance. In present work, we attempted to develop benzthiazole derivatives as lysine aminotransferase inhibitors. In our attempts, we also unexpectedly arrived at an interesting compound 21 (E)-4-(5-(2-(benzo[d]thiazol-2-yl)-2-cyanovinyl)thiophen-2-yl)benzoic acid which even though has moderate activity against persistent phase of mycobacterium, it has significant potency against active phase. In the entire series compound 22 (E)-4-(5-(2-(benzo[d]thiazol-2-yl)-2-cyanovinyl)thiophen-2-yl)isophthalic acid emerged as potent molecule with LAT IC50 of 2.62 µM. It has a significant log reduction of 2.9 and 2.3 fold against nutrient starved and biofilm forming mycobacteria. It was found to be inactive in MABA assay and M.marinum induced zebra fish model. It is also devoid of cytotoxicity. Compound 22 was also found to possess bactericidal effect which is independent of concentration and time. It was found to be effective in combination with Rifampicin in 3D granuloma model. The results are very encouraging as the hit molecule shows activity against active as well as persistent forms of tuberculosis. The identified hit needs further more pharmacokinetic and dynamic screening for development as new drug candidate.

Keywords: benzothiazole, latent tuberculosis, LAT, nutrient starvation

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Authors: Roland Benedict Reyes, Marc Edsel Ayes, Regina Berba, Cybele Lara Abad

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Background: Three AIDS-defining malignancies have been associated with the human immunodeficiency virus (HIV): Kaposi’s sarcoma, non-Hodgkin’s lymphoma, and cervical carcinoma. However, new cases of non-AIDS defining malignancies also have been increasingly associated with HIV. One of these is a rare intracranial malignancy, meningeal hemangiopericyotma. Case Description: A 32-year old HIV-positive male, not on highly active antiretroviral therapy, was admitted to our hospital due to generalized weakness and sudden onset hearing loss. Cranial MRI was done, which revealed a temporal nodule with the following considerations: granuloma, meningioma or metastases. A craniotomy was performed and the mass excised. Results from the biopsy showed meningeal hemangiopericytoma. The patient was then started on antiretroviral therapy (Lamivudine, Tenofovir, and Efavirenz) and was discharged for radiation therapy and metastatic work-up as an outpatient. On follow-up seven months later, metastatic work up revealed multiple hepatic foci not previously documented suggestive of metastasis short of biopsy sampling. Conclusions: This case of an intracranial hemangiopericytoma in an HIV-positive patient is the second case thus far presented, based on our systematic and extensive search of the literature.

Keywords: Hemangiopericytoma, Human Immunodeficiency Virus, Meningeal hemangiopericytoma, Neoplasm

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Authors: Titap Yazicioglu

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To examine the results of two different surgery in patients with severe ptosis and poor levator function. The records of 10 bilateral congenital ptosis patients, who underwent Whitnall’s sling surgery on one eyelid and frontalis sling surgery on the other were analyzed retrospectively. All patients had severe congenital ptosis(>4mm) and poor levator function (LF<4mm). Data regarding eyelid position, cosmetic outcomes, and postoperative complications were evaluated. All patients were assessed for a minimum of one year with regard to the amount of correction, residual ptosis and lagophthalmos. The study consisted of 10 patients, with an average age of 9.2±2.4 years. Preoperative diagnosis for all patients was noted as, the average LF was 3.4±0.51mm, vertical lid height was 3.5±0.52 mm and margin reflex distance-1 (MRD-1) was 0.4±0.51mm. The mean vertical lid height was measured as 7.1±0.73 mm in the frontalis sling group and 7.2±0.63 mm in the Whitnall’s sling group at the postoperative 1st month control. However, in patients with Whitnall’s sling, revision was performed with frontalis sling surgery due to failure in vertical lid height in the late postoperative period, and an average of 7.5±0.52 mm was achieved. Satisfactory results were obtained in all patients. Although postoperative lagophthalmitis developed in the frontalis sling group, none of them developed exposure keratitis. Granuloma was observed as sling infection in 2(20%) of the patients. Although Whitnall’s sling technique provides a natural look appearance without interfering with the functional result, we did not find it as successful as frontalis sling surgery in severe ptosis.

Keywords: congenital ptosis, frontalis suspension, Whitnall ligament, complications

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Authors: Ghada E. Esheba, Ghadeer F. Alharthi, Duaa A. Alhejaili, Rawan E. Hudairy, Wafaa A. Altaezi, Raghad M. Alhejaili

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Background: Inflammatory bowel disease (IBD) consists of two specific gastrointestinal disorders: ulcerative colitis (UC) and Crohn's disease (CD). Despite their distinct natures, these two diseases share many similar etiologic, clinical and pathological features, as a result, their accurate differential diagnosis may sometimes be difficult. Correct diagnosis is important because surgical treatment and long-term prognosis differ from UC and CD. Aim: This study aims to study the characteristic clinicopathological features which help in the differential diagnosis between UC and CD, and assess the disease activity in ulcerative colitis. Materials and methods: This study was carried out on 50 selected cases. The cases included 27 cases of UC and 23 cases of CD. All the cases were examined using H& E and immunohistochemically for bcl-2 expression. Results: Characteristic features of UC include: decrease in mucous content, irregular or villous surface, crypt distortion, and cryptitis, whereas the main cardinal histopathological features seen in CD were: epitheloid granuloma, transmural chronic inflammation, absence of mucin depletion, irregular surface, or crypt distortion. 3 cases of UC were found to be associated with dysplasia. UC mucosa contains fewer Bcl-2+ cells compared with CD mucosa. Conclusion: This study using multiple parameters such clinicopathological features and Bcl-2 expression as studied by immunohistochemical stain, helped to gain an accurate differentiation between UC and CD. Furthermore, this work spotted the light on the activity and different grades of UC which could be important for the prediction of relapse.

Keywords: Crohn's disease, dysplasia, inflammatory bowel disease, ulcerative colitis

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Authors: Titap Yazicioglu

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Purpose: To determine the etiological factors responsible for the eye removal surgery and to evaluate our surgical results. Material and Methods: Medical records of 226 patients, who underwent eye removal surgery, were analyzed retrospectively. Demographic information, clinical history, surgical procedure, and histopathological data were all collected. Evisceration surgery was performed under general anesthesia in all patients except tumor cases and one patient with rhino-orbital mucormycosis. The patients were followed for an average of 16.46±10.78 months and checked for the possible complications, cosmesis, and functional results.Results: 144 men, and 82 women,with a mean age of 41.78±22.6 years, were underwent enucleation (n=15) or evisceration (n=211) due to traumatic (n=169) and non-traumatic (n=57) causes. In the traumatic group, 79.8% of 169 patients were injured by penetrating and 14.2% by blunt trauma.3.6% of the patients were injured in a traffic accident, and 2.4% of them were injured by explosives. In the non-traumatic group, 40% of 25 patients had post-traumatic endophthalmitis, 32% had endophthalmitis due to corneal ulceration and melting, and 24% had endophthalmitis after cataract surgery. One patient had panophthalmitis due to rhino-orbital mucormycosis. Another cause in the non-traumatic group was glaucoma, of which 92.3% had neovascular glaucoma, and 8.7% had congenital glaucoma. Of the 14 patients who were enucleated for tumor, 35.7% had retinoblastoma, 14.3% had medulloepithelioma, 42.9% had uveal melanoma, and 7.1% had metastatic tumor from paranasal sinuses.The most common complaint in the follow-up period was discharging, seen in all prosthesis-wearing patients. 13.3% of the patients had itching due to ocular prosthesis. 4.4% of the patients were complaining about deep superior sulcus. 4.4% had pyogenic granuloma, and 17.8% had implant exposure. Conclusion: Etiological factors should be carefully evaluated, and precautions should be taken in order to reduce the devastating effect of the physical loss of the eye.

Keywords: enucleation, evisceration, ocular injury, etiology, frequency

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Authors: Dahna Alkahtani, Faryal Suraya, Fadah Alanazi

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Background: Buccal mucosal graft for urethral augmentation has surpassed other grafting options, and is now considered the standard of choice for substitution Urethroplasty. The graft has gained its popularity due to its excellent short and long-term results, easy harvesting as well as its ability in withstanding wet environments. However, although Buccal mucosal grafts are an excellent option, it is not free of complications, potential intraoral complications are bleeding, pain, swelling, injury to the nerve resulting in numbness, lip deviation or retraction. Objectives: The current study aims to evaluate the intraoral complications of buccal mucosa grafts harvested from one cheek, and used in Augmentation Urethroplasty. Methodology: The study was conducted retrospectively using the medical records of patients who underwent open augmentation urethroplasty with a buccal mucosa graft at King Khalid University Hospital, Saudi Arabia. Data collection of demographics included the type of graft used, presence or absence of strictures and its etiological factors. Pre-operative and post-operative evaluations were carried out on the subjects including the medical history, physical examination, uroflowmetry, retrograde urethrography, voiding cystourethrography and urine cultures were also noted. Further, the quality of life and complications of the procedure including the presence or occurrence of bleeding within 3-days post-procedure, the severity of pain, oral swelling after grafting, length of return to normal daily diet, painful surgical site, intake of painkillers, presence or absence of speech disturbance, numbness in the cheeks and lips were documented. Results: Thirty-two male subjects with ages ranging from 15 years to 72 years were included in the current study. Following the procedure, a hundred percent of the subjects returned to their normal daily diet by the sixth postoperative day. Further, the majority of the patients reported experiencing mild pain accounting for 61.3%, and 90.3% of the subjects reported using painkillers to control the pain. Surgical wound Pain was reportedly more common at the perineal site as 48.4% of the subjects experienced it; on the other hand, 41.9% of the patients experienced pain in the oral mucosa. The presence of speech disorders, as assessed through medical history, was found to be present in 3.2% of patients. The presence of numbness in the cheeks and lips was found in 3.2% of patients. Other complications such as parotid duct injury, delayed wound healing, non-healing wound and suture granuloma were rare as 90.3% of the subjects denied experiencing any of them, there were nonetheless reports of parotid duct injury by 6.5% of the patients, and non-healing wound by the 3.2% of patients. Conclusion: Buccal Mucosa Graft in Augmentation Urethroplasty is an ideal source of allograft, although not entirely painless; it is considerably safe with minimal intra-oral complication and undetectable strain on the patients’ quality of life.

Keywords: augmentation, buccal, graft, oral

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Authors: Manal M. Kame, Zeinab A. Demerdash, Hanan G. El-Baz, Salwa M. Hassan, Faten M. Salah, Wafaa Mansour, Olfat Hammam

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Cord blood (CB) derived Unrestricted Somatic Stem Cells (USSCs) with their multipotentiality hold great promise in liver regeneration. This work aims at evaluation of the therapeutic potentiality of USSCs in two experimental models of chronic liver injury induced either by S. mansoni infection in balb/c mice or CCL4 injection in hamsters. Isolation, propagation, and characterization of USSCs from CB samples were performed. USSCs were induced to differentiate into osteoblasts, adipocytes and hepatocyte-like cells. Cells of the third passage were transplanted in two models of liver fibrosis: (1) Twenty hamsters were induced to liver fibrosis by repeated i. p. injection of 100 μl CCl4 /hamster for 8 weeks. This model was designed as; 10 hamsters with liver fibrosis and treated with i.h. injection of 3x106 USSCs (USSCs transplanted group), 10 hamsters with liver fibrosis (pathological control group), and 10 hamsters with healthy livers (normal control group). (2) Murine chronics S.mansoni model: twenty mice were induced to liver fibrosis with S. mansoni ceracariae (60 cercariae/ mouse) using the tail immersion method and left for 12 weeks. This model was designed as; 10 mice with liver fibrosis were transplanted with i. v. injection of 1×106 USCCs (USSCs transplanted group). Other 2 groups were designed as in hamsters model. Animals were sacrificed 12 weeks after USSCs transplantation, and their liver sections were examined for detection of human hepatocyte-like cells by immunohistochemistry staining. Moreover, liver sections were examined for fibrosis level, and fibrotic indices were calculated. Sera of sacrificed animals were tested for liver functions. CB USSCs, with fibroblast-like morphology, expressed high levels of CD44, CD90, CD73 and CD105 and were negative for CD34, CD45, and HLA-DR. USSCs showed high expression of transcripts for Oct4 and Sox2 and were in vitro differentiated into osteoblasts, adipocytes. In both animal models, in vitro induced hepatocyte-like cells were confirmed by cytoplasmic expression of glycogen, alpha-fetoprotein, and cytokeratin18. Livers of USSCs transplanted group showed engraftment with human hepatocyte-like cells as proved by cytoplasmic expression of human alpha-fetoprotein, cytokeratin18, and OV6. In addition, livers of this group showed less fibrosis than the pathological control group. Liver functions in the form of serum AST & ALT level and serum total bilirubin level were significantly lowered in USSCs transplanted group than pathological control group (p < 0.001). Moreover, the fibrotic index was significantly lower (p< 0.001) in USSCs transplanted group than pathological control group. In addition liver sections, of i. v. injection of 1×106 USCCs of mice, stained with either H&E or sirius red showed diminished granuloma size and a relative decrease in hepatic fibrosis. Our experimental liver fibrosis models transplanted with CB-USSCs showed liver engraftment with human hepatocyte-like cells as well as signs of liver regeneration in the form of improvement in liver function assays and fibrosis level. These data provide hope that human CB- derived USSCs are introduced as multipotent stem cells with great potentiality in regenerative medicine & strengthens the concept of cellular therapy for the treatment of liver fibrosis.

Keywords: cord blood, liver fibrosis, stem cells, transplantation

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