Search results for: vasodilation

Authors: Lokesh Bhatt, Jayesh Rathod

Abstract:

Hypertension is one of the most prevalent cardiovascular disorder. It is responsible for several other cardiovascular disorders. Although many drugs are available for the treatment of hypertension, still a large population has uncontrolled blood pressure. Thus there is an unmet need for new therapeutic approaches for the same. Fruit juice of Citrus paradise contains several flavonoids with vasodilatory activity. We hypothesized that alcoholic extract of Citrus paradise, which contains flavonoids, might attenuate hypertension. The objective of the present study was to evaluate the antihypertensive activity of alcoholic extract of Citrus paradise fruit juice in rats. Hypertension was induced using one clip one kidney model in rats. The renal artery was occluded for 4 h after removal of one kidney. Once stabilized, the ganglionic blockade was performed followed by removal of the arterial clip from the kidney. Removal of clip resulted in an increase in blood pressure which is due to release of renin from the kidney. Alcoholic extract of Citrus paradise fruit juice was then administered at 50 mg/kg and 100 mg/kg dose by intravenous injection. Blood pressure was monitored continuously. Alcoholic extract of Citrus paradise fruit juice reduced hypertension in dose-dependent manner. Antihypertensive activity was found to be associated with vasodilation. The results of the present study showed antihypertensive potential of alcoholic extract of Citrus paradise fruit juice.

Keywords: citrus paradise, alcoholic extract, one clip one kidney model, vasodilation

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Authors: Hossam M. Abdallah, Ali M. El-Halawany, Gamal A. Mohamed, Khalid Z. Alshali, Zainy M. Banjar, Hany A. El-Bassossy

Abstract:

Hypertension and vascular dysfunction are major components and complications of many diseases like metabolic syndrome. In addition, vascular dysfunction is considered the initial step in diabetic atherosclerosis, the main etiology for mortality and a great percent of morbidity in diabetic patients. In spite of the significant developments in antidiabetic therapy, diabetic complications, particularly seen in long-term diabetes, continue to be seriously deleterious. Herbal drugs are prescribed widely in treatment of different aliment because of their effectiveness, fewer side effects and relatively low cost. Nine plants belong to five different families grown in Kingdom of Saudi Arabia were evaluated for their effect on exaggerated vasoconstriction and impaired relaxation in aortae isolated from metabolic syndrome rats. The aerial parts of Onopordum ambiguum Fresen. (OA), Astragalus abyssinicus Steud. (AA), Pulicaria Arabica Cass. (PA), Echinops sheilae Kit Tan (ES), Aizoon canariense L. (AC), Cleome viscosa L. (CV), Chrozophora oblongifolia (Delile) A.Juss. ex Spreng (CO), Centaurea pseudosinaica Mouterde (CP) and Tephrosia nubica Baker (TN) were dried and extracted with methanol. The effect of thirty minute incubation with the total extracts (10-330 µg/ml) or their fractions on the exaggerated vasoconstriction response to phenylephrine (10nM to 10microM) and impaired vasodilation to acetylcholine (10-330 µg /ml) of aortae isolated from metabolic syndrome animals was studied. Incubating aortae isolated from metabolic syndrome animals with total methanol extract of OA, AA, PA, AC, CV, and TN at concentrations (10-330 microgram/ml) in the organ bath led to concentration dependent alleviation of exaggerated vasoconstriction response to phenylephrine without having beneficial effect on impaired vasodilation to acetylcholine. In conclusion, addition of OA, AA, PA, AC, CV and TN to the standard therapies may provide superior means to alleviate the associated vascular complications.

Keywords: vascular dysfunction, exaggerated vasoconstriction, metabolic syndrome, Saudi plants

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Authors: Irina Mizeva, Elena Potapova, Viktor Dremin, Mikhail Mezentsev, Valeri Shupletsov

Abstract:

The local tissue perfusion is regulated by the microvascular tone which is under the control of a number of physiological mechanisms. Laser Doppler flowmetry (LDF) together with wavelet analyses is the most commonly used technique to study the regulatory mechanisms of cutaneous microcirculation. External factors such as temperature, local pressure of the probe on the skin, etc. influence on the blood flow characteristics and are used as physiological tests to evaluate microvascular regulatory mechanisms. Local probe pressure influences on the microcirculation parameters measured by optical methods: diffuse reflectance spectroscopy, fluorescence spectroscopy, and LDF. Therefore, further study of probe pressure effects can be useful to improve the reliability of optical measurement. During pressure tests variation of the mean perfusion measured by means of LDF usually is estimated. An additional information concerning the physiological mechanisms of the vascular tone regulation system in response to local pressure can be obtained using spectral analyses of LDF samples. The aim of the present work was to develop protocol and algorithm of data processing appropriate for study physiological response to the local pressure test. Involving 6 subjects (20±2 years) and providing 5 measurements for every subject we estimated intersubject and-inter group variability of response of both averaged and oscillating parts of the LDF sample on external surface pressure. The final purpose of the work was to find special features which further can be used in wider clinic studies. The cutaneous perfusion measurements were carried out by LAKK-02 (SPE LAZMA Ltd., Russia), the skin loading was provided by the originally designed device which allows one to distribute the pressure around the LDF probe. The probe was installed on the dorsal part of the distal finger of the index figure. We collected measurements continuously for one hour and varied loading from 0 to 180mmHg stepwise with a step duration of 10 minutes. Further, we post-processed the samples using the wavelet transform and traced the energy of oscillations in five frequency bands over time. Weak loading leads to pressure-induced vasodilation, so one should take into account that the perfusion measured under pressure conditions will be overestimated. On the other hand, we revealed a decrease in endothelial associated fluctuations. Further loading (88 mmHg) induces amplification of pulsations in all frequency bands. We assume that such loading leads to a higher number of closed capillaries, higher input of arterioles in the LDF signal and as a consequence more vivid oscillations which mainly are formed in arterioles. External pressure higher than 144 mmHg leads to the decrease of oscillating components, after removing the loading very rapid restore of the tissue perfusion takes place. In this work, we have demonstrated that local skin loading influence on the microcirculation parameters measured by optic technique; this should be taken into account while developing portable electronic devices. The proposed protocol of local loading allows one to evaluate PIV as far as to trace dynamic of blood flow oscillations. This study was supported by the Russian Science Foundation under project N 18-15-00201.

Keywords: blood microcirculation, laser Doppler flowmetry, pressure-induced vasodilation, wavelet analyses blood

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Authors: F. Saleh, F. Lyall, A. Abdulsid, L. Marks

Abstract:

Background: Labour in human is a complex biological process that involves interactions of neurological, hormonal and inflammatory pathways, with the placenta being a key regulator of these pathways. It is known that uterine contractions and labour pain cause physiological changes in gene expression in maternal and fetal blood, and in placenta during labour. Oxidative and inflammatory stress pathways are implicated in labour and they may cause alteration of placental gene expression. Additionally, in placental tissues, labour increases the expression of genes involved in placental oxidative stress, inflammatory cytokines, angiogenic regulators and apoptosis. Recently, Hydrogen Sulphide (H2S) has been considered as an endogenous gaseous mediator which promotes vasodilation and exhibits cytoprotective anti-inflammatory properties. The endogenous H2S is synthesised predominantly by two enzymes: cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE). As the H2S pathway has anti-oxidative and anti-inflammatory characteristics thus, we hypothesised that the expression of CBS and CSE in placental tissues would alter during labour. Methods: CBS and CSE expressions were examined in placentas using western blotting and RT-PCR in inner, middle and outer placental zones in placentas obtained from healthy non labouring women who delivered by caesarian section. These were compared with the equivalent zone of placentas obtained from women who had uncomplicated labour and delivered vaginally. Results: No differences in CBS and CSE mRNA or protein levels were found between the different sites within placentas in either the labour or non-labour group. There were no significant differences in either CBS or CSE expression between the two groups at the inner site and middle site. However, at the outer site there was a highly significant decrease in CBS protein expression in the labour group when compared to the non-labour group (p = 0.002). Conclusion: To the best of author’s knowledge, this is the first report to suggest that, CBS is expressed in a spatial manner within the human placenta. Further work is needed to clarify the precise function and mechanism of this spatial regulation although it is likely that inflammatory pathways regulation is a complex process in which this plays a role.

Keywords: anti-inflammatory, hydrogen sulphide, labour, oxidative stress

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Authors: Takuya Suzuki, Atsushi Shirai, Takashi Seki

Abstract:

Acupuncture therapy is one of the treatments in traditional Chinese medicine. Recently, some reports have shown the effectiveness of acupuncture. However, its full acceptance has been hindered by the lack of understanding on mechanism of the therapy. Acupuncture applied to Zusanli (ST-36) enhances blood flow volume in superior mesenteric artery (SMA), yielding peripheral vascular resistance – regulated blood flow of SMA dominated by the parasympathetic system and inhibition of sympathetic system. In this study, a lumped-parameter approximation model of blood flow in the systemic arteries was developed. This model was extremely simple, consisting of the aorta, carotid arteries, arteries of the four limbs and SMA, and their peripheral vascular resistances. Here, the individual artery was simplified to a tapered tube and the resistances were modelled by a linear resistance. We numerically investigated contribution of the peripheral vascular resistance of SMA to the systemic blood distribution using this model. In addition to the upstream end of the model, which correlates with the left ventricle, two types of boundary condition were applied; mean left ventricular pressure which correlates with blood pressure (BP) and mean cardiac output which corresponds to cardiac index (CI). We examined it to reproduce the experimentally obtained hemodynamic change, in terms of the ratio of the aforementioned hemodynamic parameters from their initial values before the acupuncture, by regulating the peripheral vascular resistances and the upstream boundary condition. First, only the peripheral vascular resistance of SMA was changed to show contribution of the resistance to the change in blood flow volume in SMA, expecting reproduction of the experimentally obtained change. It was found, however, this was not enough to reproduce the experimental result. Then, we also changed the resistances of the other arteries together with the value given at upstream boundary. Here, the resistances of the other arteries were changed simultaneously in the same amount. Consequently, we successfully reproduced the hemodynamic change to find that regulation of the upstream boundary condition to the value experimentally obtained after the stimulation is necessary for the reproduction, though statistically significant changes in BP and CI were not observed in the experiment. It is generally known that sympathetic and parasympathetic tones take part in regulation of whole the systemic circulation including the cardiac function. The present result indicates that stimulation to ST-36 could induce vasodilation of peripheral circulation of SMA and vasoconstriction of that of other arteries. In addition, it implies that experimentally obtained small changes in BP and CI induced by the acupuncture may be involved in the therapeutic response.

Keywords: acupuncture, hemodynamics, lumped-parameter approximation, modeling, systemic vascular resistance

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Authors: Ammar Boudaka, Maryam Al-Suleimani, Hajar BaOmar, Intisar Al-Lawati, Fahad Zadjali

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Background: Hypertension is increasingly becoming a matter of medical and public health importance. The maintenance of normal blood pressure requires a balance between cardiac output and total peripheral resistance. The endothelium, through the release of vasodilating factors, plays an important role in the control of total peripheral resistance and hence blood pressure homeostasis. Transient Receptor Potential Vanilloid type 4 (TRPV4) is a mechanosensitive non-selective cation channel that is expressed on the endothelium and contributes to endothelium-mediated vasodilation. So far, no data are available about the morphological and functional status of this channel in hypertensive cases. Objectives: This study aimed to investigate whether there is any difference in the morphological and functional features of TRPV4 in the mesenteric artery of normotensive and hypertensive rats. Methods: Functional feature of TRPV4 in four experimental animal groups: young and adult Wistar-Kyoto rats (WKY-Y and WKY-A), young and adult spontaneously hypertensive rats (SHR-Y and SHR-A), was studied by adding 5 µM 4αPDD (TRPV4 agonist) to mesenteric arteries mounted in a four-chamber wire myograph and pre-contracted with 4 µM phenylephrine. The 4αPDD-induced response was investigated in the presence and absence of 1 µM HC067047 (TRPV4 antagonist), 100 µM L-NAME (nitric oxide synthase inhibitor), and endothelium. The morphological distribution of TRPV4 in the wall of rat mesenteric arteries was investigated by immunostaining. Real-time PCR was used in order to investigate mRNA expression level of TRPV4 in the mesenteric arteries of the four groups. The collected data were expressed as mean ± S.E.M. with n equal to the number of animals used (one vessel was taken from each rat). To determine the level of significance, statistical comparisons were performed using the student’s t-test and considered to be significantly different at p<0.05. Results: 4αPDD induced a relaxation response in the mesenteric arterial preparations (WKY-Y: 85.98% ± 4.18; n = 5) that was markedly inhibited by HC067047 (18.30% ± 2.86; n= 5; p<0.05), endothelium removal (19.93% ± 1.50; n = 5; p<0.05) and L-NAME (28.18% ± 3.09; n = 5; p<0.05). The 4αPDD-induced relaxation was significantly lower in SHR-Y compared to WKY-Y (SHR-Y: 70.96% ± 3.65; n = 6, WKY-Y: 85.98% ± 4.18; n = 5-6, p<0.05. Moreover, the 4αPDD-induced response was significantly lower in WKY-A than WKY-Y (WKY-A: 75.58 ± 1.30; n = 5, WKY-Y: 85.98% ± 4.18; n = 5, p<0.05). Immunostaining study showed immunofluorescent signal confined to the endothelial layer of the mesenteric arteries. The expression of TRPV4 mRNA in SHR-Y was significantly lower than in WKY-Y (SHR-Y; 0.67RU ± 0.34; n = 4, WKY-Y: 2.34RU ± 0.15; n = 4, p<0.05). Furthermore, TRPV4 mRNA expression in WKY-A was lower than its expression in WKY-Y (WKY-A: 0.62RU ± 0.37; n = 4, WKY-Y: 2.34RU ± 0.15; n = 4, p<0.05). Conclusion: Stimulation of TRPV4, which is expressed on the endothelium of rat mesenteric artery, triggers an endothelium-mediated relaxation response that markedly decreases with hypertension and growing up changes due to downregulation of TRPV4 expression.

Keywords: hypertension, endothelium, mesenteric artery, TRPV4

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Authors: Nermeen Elbeltagy, Helmy abd Elsatar, Sara Hassan, Mohamed Darwish

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Introduction: with the inial appearance in Wuhan, China, in December 2019, the coronavirus disease-related respiratory infection (COVID-19) has rapidly spread among people all over the world. The WHO considered it a pandemic in March 2020. The severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV) outbreaks have proved that pregnant females as well as their fetuses are exposed to adverse outcomes, including high rates of intensive care unit (ICU) admission and case fatality. Physiological changes occurring during pregnancy such as the increased transverse diameter of the thoracic cage as well as the elevation of the diaphragm can expose the mother to severe infections because of her decreased tolerance for hypoxia. Furthermore, vasodilation and changes in lung capacity can cause mucosal edema and an increase in upper respiratory tract secretions. In addition, the increased susceptibility to infection is enhanced by changes in cellmediated immunity. Aim of the work: to study the effect of COVID-19 on pregnant females admitted to El-Shatby Maternity University Hospital regarding maternal antepartum, intrapartum and postpartum adverse effects on the mothers and their neonates. Method: A retrospective cohort study was done between October 2020 and October 2022. Maternal characteristics and associated health conditions of COVID-19 positive parents were investigated. Also, the severity of their conditions and me of infection (first or second or third trimester)were explored. Cases were diagnosed based on presence of symptoms suggestive of COVID-19, laboratory tests (other than PCR) and radiological findings.all cases were confirmed by positive PCR test results. Results: The most common adverse maternal outcomes were pre-term labor (11.6%) followed by premature rupture of membranes (5.7%), post-partum hemorrhage (5.4%), preeclampsia (5.0%) and placental abrupon (4.3%). One sixth of the neonates of the studied paents were admied to NICUs and 6.5% of them had respiratory distress with no neonatal deaths. The majority of neonates (85.4%) had a birth weight of 2500- 4000g (normal range). Most of the neonates (77.9%) had an APGAR score of equal or more than 7 in 5 minutes. Conclusion: the most common comorbidity that might increase the incidence of COVID-19 before pregnancy were diabetes, cardiac disorders/ chronic hypertension and chronic obstructive lung diseases (non-asthma). During pregnancy, anemia followed by gestational diabetes and pre-eclampsia/gestational hypertension were the most prevalent comorbidity. So, severity of infection can be reduced by good antenatal care.

Keywords: COVID-19, pregnancy outcome, complicated pregnancy., COVID in Egypt

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Authors: Tina Naser Torabi

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Prevalence of allergy is affected by different factors according to its base and seasonal weather changes, and it also needs various treatments.Although reasons of allergy existence are not clear but generally, allergens cause reaction between antigen and antibody because of their antigenic traits. In this state, allergens cause immune system to make mistake and identify safe material as threat, therefore function of immune system impaired because of histamine secretion. There are different reasons for allergy, but herbal reasons are on top of the list, although animal causes cannot be ignored. Important point is that allergenic compounds, cause making dedicated antibody, so in general every kind of allergy is different from the other one. Therefore, most of the plants in herbal allergenic category can cause various allergies for human beings, such as respiratory allergies, nutritional allergies, injection allergies, infection allergies, touch allergies, that each of them show different symptoms based on the reason of allergy and also each of them requires different prevention and treatment. Geographical condition is another effective factor in allergy. Seasonal changes, weather condition, herbal coverage variety play important roles in different allergies. It goes without saying that humid climate and herbal coverage variety in different seasons especially spring cause most allergies in human beings in Iran and India that are discussed in this article. These two countries are good choices for allergy prevalence because of their condition, various herbal coverage, human and animal factors. Hay fever is one of the allergies, although the reasons of its prevalence are unknown yet. It is one of the most popular allergies in Iran and India because of geographical, human, animal and herbal factors. Hay fever is on top of the list in these two countries. Significant point about these two countries is that herbal factor is the most important factor in prevalence of hay fever. Variety of herbal coverage especially in spring during herbal pollination is the main reason of hay fever prevalence in these two countries. Based on the research result of Pharmacognosy and Phytochemistry, pollination of some plants in spring is major reason of hay fever prevalence in these countries. If airborne pollens in pollination season enter the human body through air, they will cause allergic reactions in eyes, nasal mucosa, lungs, and respiratory system, and if these particles enter the body of potential person through food, they will cause allergic reactions in mouth, stomach, and other digestive systems. Occasionally, chemical materials produced by human body such as Histamine cause problems like: developing of nasal polyps, nasal blockage, sleep disturbance, risk of asthma developing, blood vasodilation, sneezing, eye tears, itching and swelling of eyes and nasal mucosa, Urticaria, decrease in blood pressure, and rarely trauma, anesthesia, anaphylaxis and finally death. This article is going to study the reasons of hay fever prevalence in Iran and India and presents prevention and treatment Method from Phytochemistry and Pharmocognocy point of view by using local natural products in these two countries.

Keywords: hay fever, India, Iran, natural treatment, phytochemistry

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Authors: Vinod Kumar

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Background: Tissue Plasminogen Activator (tPA) showed a level 1 benefit in acute stroke (within 3-6 hrs). Intracarotid sodium nitroprusside (ICSNP) has been studied in this context with a wide treatment window, fast recovery and affordability. This work proposes two mechanisms for acute cases and one mechanism for chronic cases, which are interrelated, for physiological recovery. a)Retrograde Neurotransmission (acute cases): 1)Normal excitatory impulse: at the synaptic level, glutamate activates NMDA receptors, with nitric oxide synthetase (NOS) on the postsynaptic membrane, for further propagation by the calcium-calmodulin complex. Nitric oxide (NO, produced by NOS) travels backward across the chemical synapse and binds the axon-terminal NO receptor/sGC of a presynaptic neuron, regulating anterograde neurotransmission (ANT) via retrograde neurotransmission (RNT). Heme is the ligand-binding site of the NO receptor/sGC. Heme exhibits > 10,000-fold higher affinity for NO than for oxygen (the 10,000-fold effect) and is completed in 20 msec. 2)Pathological conditions: normal synaptic activity, including both ANT and RNT, is absent. A NO donor (SNP) releases NO from NOS in the postsynaptic region. NO travels backward across a chemical synapse to bind to the heme of a NO receptor in the axon terminal of a presynaptic neuron, generating an impulse, as under normal conditions. b)Vasospasm: (acute cases) Perforators show vasospastic activity. NO vasodilates the perforators via the NO-cAMP pathway. c)Long-Term Potentıatıon (LTP): (chronic cases) The NO–cGMP-pathway plays a role in LTP at many synapses throughout the CNS and at the neuromuscular junction. LTP has been reviewed both generally and with respect to brain regions specific for memory/learning. Aims/Study Des’gn: The principles of “generation of impulses from the presynaptic region to the postsynaptic region by very potent RNT (10,000-fold effect)” and “vasodilation of arteriolar perforators” are the basis of the authors’ hypothesis to treat stroke cases. Case-control prospective study. Mater’als And Methods: The experimental population included 82 stroke patients (10 patients were given control treatments without superfusion or with 5% dextrose superfusion, and 72 patients comprised the ICSNP group). The mean time for superfusion was 9.5 days post-stroke. Pre- and post-ICSNP status was monitored by NIHSS, MRI and TCD. Results: After 90 seconds in the ICSNP group, the mean change in the NIHSS score was a decrease of 1.44 points, or 6.55%; after 2 h, there was a decrease of 1.16 points; after 24 h, there was an increase of 0.66 points, 2.25%, compared to the control-group increase of 0.7 points, or 3.53%; at 7 days, there was an 8.61-point decrease, 44.58%, compared to the control-group increase of 2.55 points, or 22.37%; at 2 months in ICSNP, there was a 6.94-points decrease, 62.80%, compared to the control-group decrease of 2.77 points, or 8.78%. TCD was documented and improvements were noted. Conclusions: ICSNP is a swift-acting drug in the treatment of stroke, acting within 90 seconds on day 9.5 post-stroke with a small decrease after 24 hours. The drug recovers from this decrease quickly.

Keywords: brain infarcts, intracarotid sodium nitroprusside, perforators, vasodilatıons, retrograde transmission, the 10, 000-fold effect

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Authors: V. K. Tewari, M. Hussain, H. K. D. Gupta

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Background: Nitric Oxide Donars (NODs) (intrathecal sodium nitroprusside (ITSNP) and oral tadalafil 20mg post ITSNP) has been studied in this context in cerebral palsy patients for fast recovery. This work proposes two mechanisms for acute cases and one mechanism for chronic cases, which are interrelated, for physiological recovery. a) Retrograde Neurotransmission (acute cases): 1) Normal excitatory impulse: at the synaptic level, glutamate activates NMDA receptors, with nitric oxide synthetase (NOS) on the postsynaptic membrane, for further propagation by the calcium-calmodulin complex. Nitric oxide (NO, produced by NOS) travels backward across the chemical synapse and binds the axon-terminal NO receptor/sGC of a presynaptic neuron, regulating anterograde neurotransmission (ANT) via retrograde neurotransmission (RNT). Heme is the ligand-binding site of the NO receptor/sGC. Heme exhibits > 10,000-fold higher affinity for NO than for oxygen (the 10,000-fold effect) and is completed in 20 msec. 2) Pathological conditions: normal synaptic activity, including both ANT and RNT, is absent. A NO donor (SNP) releases NO from NOS in the postsynaptic region. NO travels backward across a chemical synapse to bind to the heme of a NO receptor in the axon terminal of a presynaptic neuron, generating an impulse, as under normal conditions. b) Vasopasm: (acute cases) Perforators show vasospastic activity. NO vasodilates the perforators via the NO-cAMP pathway. c) Long-Term Potentiation (LTP): (chronic cases) The NO–cGMP-pathway plays a role in LTP at many synapses throughout the CNS and at the neuromuscular junction. LTP has been reviewed both generally and with respect to brain regions specific for memory/learning. Aims/Study Design: The principles of “generation of impulses from the presynaptic region to the postsynaptic region by very potent RNT (10,000-fold effect)” and “vasodilation of arteriolar perforators” are the basis of the authors’ hypothesis to treat cerebral palsy cases. Case-control prospective study. Materials and Methods: The experimental population included 82 cerebral palsy patients (10 patients were given control treatments without NOD or with 5% dextrose superfusion, and 72 patients comprised the NOD group). The mean time for superfusion was 5 months post-cerebral palsy. Pre- and post-NOD status was monitored by Gross Motor Function Classification System for Cerebral Palsy (GMFCS), MRI, and TCD studies. Results: After 7 days in the NOD group, the mean change in the GMFCS score was an increase of 1.2 points mean; after 3 months, there was an increase of 3.4 points mean, compared to the control-group increase of 0.1 points at 3 months. MRI and TCD documented the improvements. Conclusions: NOD (ITSNP boosts up the recovery and oral tadalafil maintains the recovery to a well-desired level) acts swiftly in the treatment of CP, acting within 7 days on 5 months post-cerebral palsy either of the three mechanisms.

Keywords: cerebral palsy, intrathecal sodium nitroprusside, oral tadalafil, perforators, vasodilations, retrograde transmission, the 10, 000-fold effect, long-term potantiation

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