ABSTRACT
Single fibre electromyography is the most sensitive neurophysiological test for the diagnosis of neuromuscular junction disorders, particularly myasthenia gravis. The study aimed at establishing concentric needle (CN) normal jitter values for voluntarily activated orbicularis-oculi (V-OOc) & Frontalis (V-FRO) muscles in Sudanese population. 57 healthy volunteers (20 males & 37 females) were included in the study (mean Age 43.6 ± 14.2 years, range 18-70 years). V-OOc and V-FRO were tested in the same individual using CN. Jitter values were expressed as the mean consecutive difference (MCD) of 30 potential pairs in microseconds. The mean jitter, mean individual fibre pairs jitter & mean outliers jitter values with (upper 95% Confidence Limit-CL) for [OOc] were [26.9 ± 3.3 (31.97), 26.1 ± 8.9 (41.8) & 38.5 ± 5.7 (49.0) µs] & for [FRO] were [27.1 ± 3.0 (31.32), 26.4 ± 9.4 (42.9) & 39.9 ± 5 (49.2) µs] respectively. The suggested practical upper limits for mean jitter & for outliers were (32, 49 µs) for OOc & (31, 49 µs) for FRO. Our CN-jitter values were within the range of the few published studies. The study was unique in that it established and compared between CN reference jitter values of two voluntarily activated facial muscles (V-OOc & V-FRO) in the same individual in large number of healthy subjects.
Subject(s)
Eyelids/physiology , Muscle Contraction/physiology , Muscle Fibers, Skeletal/physiology , Myasthenia Gravis/diagnosis , Neuromuscular Junction/physiology , Adolescent , Adult , Aged , Blinking/physiology , Cross-Sectional Studies , Electric Stimulation , Electrodes , Electromyography/methods , Facial Muscles/physiology , Female , Forehead/physiology , Healthy Volunteers , Humans , Male , Middle Aged , Myasthenia Gravis/physiopathology , Prospective Studies , Sudan , Young AdultABSTRACT
A recent symposium and workshop in Khartoum, the capital of the Republic of Sudan, brought together broad expertise from three universities to address the current burden of communicable and non-communicable diseases facing the Sudanese healthcare system. These meetings identified common challenges that impact the burden of diseases in the country, most notably gaps in data and infrastructure which are essential to inform and deliver effective interventions. Non-communicable diseases, including obesity, type 2 diabetes, renal disease and cancer are increasing dramatically, contributing to multimorbidity. At the same time, progress against communicable diseases has been slow, and the burden of chronic and endemic infections remains considerable, with parasitic diseases (such as malaria, leishmaniasis and schistosomiasis) causing substantial morbidity and mortality. Antimicrobial resistance has become a major threat throughout the healthcare system, with an emerging impact on maternal, neonatal and paediatric populations. Meanwhile, malnutrition, micronutrient deficiency and poor perinatal outcomes remain common and contribute to a lifelong burden of disease. These challenges echo the United Nations (UN) sustainable development goals and concentrating on them in a unified strategy will be necessary to address the national burden of disease. At a time when the country is going through societal and political transition, we draw focus on the country and the need for resolution of its healthcare needs.
ABSTRACT
INTRODUCTION: Hereditary spastic paraplegias (HSPs) are heterogeneous neurodegenerative disorders characterized by progressive lower limb weakness and spasticity as core symptoms of the degeneration of the corticospinal motor neurons. Even after exclusion of infectious and toxic mimickers of these disorders, the definitive diagnosis remains tricky, mainly in sporadic forms, as there is significant overlap with other disorders. Since their first description, various attempts failed to reach an appropriate classification. This was due to the constant expansion of the clinical spectrum of these diseases and the discovery of new genes, a significant number of them was involved in overlapping diseases. Areas covered: In this perspective review, an extensive literature study was conducted on the historical progress of HSP research. We also revised the previous and the current classifications of HSP and the closely related neurogenetic disorders and analyzed the areas of overlap. Expert opinion: There is undeniable need for objective case definition and reclassification of all neurogenetic disorders including HSPs, a prerequisite to improve patient follow-up, biomarker identification and develop therapeutics. The challenge is to understand why mutations can give rise to multiple phenotypic presentations along this spectrum of diseases in which the corticospinal tract is affected.
Subject(s)
Spastic Paraplegia, Hereditary/classification , Spastic Paraplegia, Hereditary/diagnosis , HumansABSTRACT
Hydrogen sulfide (H2S) is an endogenously produced gaseous messenger that participates in regulation of cardiovascular functions. This study evaluates the possible protective effect of H2S in cardiovascular dysfunction induced by cecal ligation and puncture (CLP) in rats. After 24 h of induction of CLP, heart rate (HR), mortality, cardiac and inflammation biomarkers (creatine kinase-MB (CK-MB) isozyme, cardiac troponin I (cTnI), C-reactive protein (CRP), and lactate dehydrogenase (LDH)), in vitro vascular reactivity, histopathological examination, and oxidative biomarkers (malondialdehyde (MDA), reduced glutathione (GSH), and superoxide dismutase (SOD)) were determined. CLP induced elevations in HR, mortality, serum CK-MB, cTnI, CRP, and LDH, in addition to impaired aortic contraction to potassium chloride and phenylephrine and relaxation to acetylcholine without affecting sodium nitroprusside responses. Moreover, CLP increased cardiac and aortic MDA and decreased SOD, without affecting GSH and caused a marked subserosal and interstitial inflammation in endocardium. Sodium hydrosulfide, but not the irreversible inhibitor of H2S synthesis dl-propargyl glycine, protected against CLP-induced changes in HR, mortality, cardiac and inflammatory biomarkers, oxidative stress, and myocardium histopathological changes without affecting vascular dysfunction. Our results confirm that H2S can attenuate CLP-induced cardiac, but not vascular, dysfunction possibly through its anti-inflammatory and antioxidant effects.
Subject(s)
Cardiotonic Agents/pharmacology , Hydrogen Sulfide/pharmacology , Animals , Aorta, Thoracic/drug effects , Aorta, Thoracic/physiopathology , Biomarkers/metabolism , C-Reactive Protein/analysis , Cecum/injuries , Cecum/surgery , Creatine Kinase, MB Form/blood , Glutathione/metabolism , Heart/drug effects , Heart/physiopathology , Heart Rate/drug effects , L-Lactate Dehydrogenase/blood , Ligation , Male , Malondialdehyde/metabolism , Myocardium/metabolism , Rats, Sprague-Dawley , Superoxide Dismutase/metabolism , Troponin I/bloodABSTRACT
There is a large body of evidence that nitric oxide (NO) formation is implicated in mediating silica-induced pulmonary fibrosis. As a reactive free radical, NO may not only contribute to lung parenchymal tissue injury but also has the ability to combine with superoxide and form a highly reactive toxic species peroxynitrite that can induce extensive cellular toxicity in the lung tissues. This study aimed to explore the effect of agmatine, a known NO synthase inhibitor, on silica-induced pulmonary fibrosis in rats. Male Sprague Dawley rats were treated with agmatine for 60 days following a single intranasal instillation of silica suspension (50 mg in 0.1 ml saline/rat). The results revealed that agmatine attenuated silica-induced lung inflammation as it decreased the lung wet/dry weight ratio, protein concentration, and the accumulation of the inflammatory cells in the bronchoalveolar lavage fluid. Agmatine showed antifibrotic activity as it decreased total hydroxyproline content of the lung and reduced silica-mediated lung inflammation and fibrosis in lung histopathological specimen. In addition, agmatine significantly increased superoxide dismutase (p < 0.001) and reduced glutathione (p < 0.05) activities with significant decrease in the lung malondialdehyde (p < 0.001) content as compared to the silica group. Agmatine also reduced silica-induced overproduction of pulmonary nitrite/nitrate as well as tumor necrosis factor α. Collectively, these results demonstrate the protective effects of agmatine against the silica-induced lung fibrosis that may be attributed to its ability to counteract the NO production, lipid peroxidation, and regulate cytokine effects.
Subject(s)
Agmatine/pharmacology , Enzyme Inhibitors/pharmacology , Lung/drug effects , Nitric Oxide Synthase/antagonists & inhibitors , Nitric Oxide/metabolism , Pulmonary Fibrosis/prevention & control , Silicon Dioxide , Animals , Biomarkers/metabolism , Bronchoalveolar Lavage Fluid/chemistry , Bronchoalveolar Lavage Fluid/cytology , Cytoprotection , Disease Models, Animal , Glutathione/metabolism , Hydroxyproline/metabolism , Lipid Peroxidation/drug effects , Lung/enzymology , Lung/pathology , Male , Malondialdehyde/metabolism , Nitrates/metabolism , Nitric Oxide Synthase/metabolism , Nitrites/metabolism , Pneumonia/chemically induced , Pneumonia/enzymology , Pneumonia/prevention & control , Pulmonary Edema/chemically induced , Pulmonary Edema/enzymology , Pulmonary Edema/prevention & control , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/enzymology , Pulmonary Fibrosis/pathology , Rats, Sprague-Dawley , Superoxide Dismutase/metabolism , Time FactorsABSTRACT
BACKGROUND: Mutations in the PTEN-induced putative kinase 1 (PINK1) gene at 1p36 have been involved in autosomal recessive early-onset parkinsonism. OBJECTIVE: To describe the clinical and genetic features of the largest kindred reported to date with early-onset parkinsonism associated with the PINK1 gene. DESIGN: Clinical and genetic study. SETTING: Collaborative study. Patients Eight patients from Sudan with particularly early onset (ages 9-17 years) and phenotypes varying from dopa-responsive dystonia-like to typical early-onset parkinsonism. MAIN OUTCOME MEASURES: The PINK1 genotype and Parkinson disease status of all available family members. RESULTS: The disease was caused by a novel mutation, p.A217D, located in the highly conserved adenosine triphosphate orientation site of the PINK1 kinase domain. CONCLUSION: This study extends the phenotypic and molecular spectrum of the PINK1 gene and the geographic origin of patients with PINK1 gene mutations.
Subject(s)
Adenosine Triphosphate/metabolism , Family Health , Mutation , Parkinsonian Disorders/genetics , Protein Kinases/genetics , Adolescent , Adult , Age of Onset , Alanine/genetics , Amino Acid Sequence , Aspartic Acid/genetics , DNA Mutational Analysis , Female , Genetic Predisposition to Disease , Humans , Male , Middle Aged , SudanABSTRACT
Androgenic-anabolic steroids (AAS) are widely abused by athletes and this abuse has been associated with many serious circulatory events including sudden cardiac death, myocardial infarction and cardiac hypertrophy. The effect of chronic treatment for 16 weeks with testosterone (25mg(-1)kg(-1)week(-1)) and nandrolone (50mg(-1)kg(-1)week(-1)) on serum lipids of male hypercholesterolemic New Zealand rabbits was investigated. The responses of isolated rabbit aortic rings to some vasoconstrictors (epinephrine, serotonin and endothelin-1) and vasodilators (adenosine and sodium nitroprusside) were also measured after treatment. Testosterone and nandrolone significantly reduced HDL-cholesterol levels, potentiated vasoconstriction responses to epinephrine, serotonin and endothelin-1, and attenuated vasorelaxant responses to sodium nitroprusside in rabbits. Nandrolone also caused a significant increase in LDL-cholesterol levels. No significant changes in adenosine relaxation were found in rabbits. The results of the present study showed that the abuse of AAS in presence of hypercholesterolemia can enhance atherogenicity and vasospasm as well as attenuation of vasorelaxation. Therefore the abuse of AAS is harmful to the vascular system and should be prohibited.
Subject(s)
Hypercholesterolemia/blood , Nandrolone/pharmacology , Testosterone/pharmacology , Vasoconstriction/drug effects , Vasodilation/drug effects , Animals , Dose-Response Relationship, Drug , Male , Nandrolone/toxicity , Rabbits , Substance-Related Disorders , Testosterone/toxicity , Vasoconstriction/physiology , Vasodilation/physiologyABSTRACT
1. The secretion rate of bicarbonate by the isolated saline-perfused cat pancreas was linearly related to the bicarbonate concentration of the arterial inflow at constant PCO2 and at high volume rates of secretion. 2. Pancreatic bicarbonate secretion was independent of arterial inflow pH at constant bicarbonate concentrations when the pH was manipulated by alterations in the PCO2 at high volume rates of secretion. 3. A small but statistically significant linear relationship existed between the pH of the arterial inflow and bicarbonate secretion at constant PCO2 after inhibition of carbonic anhydrase by acetazolamide. Under the same conditions no relationship was found between bicarbonate secretion and arterial inflow pH when the perfusate bicarbonate concentration was kept constant and the PCO2 varied. 4. When the volume rate of secretion was reduced by about 60-70% of maximum no relationship was found to exist between arterial inflow pH and bicarbonate secretion at constant bicarbonate concentration in the perfusate. There was also no relationship between inflow pH and bicarbonate secretion at constant PCO2 down to a pH of 7.3 until the bicarbonate concentration of the perfusate was reduced below 10 mM, when the secretion rate fell off rapidly. 5. A linear relationship was found to exist between the volume rate of secretion and the PCO2 of the pancreatic juice and the output of lactate both in the isolated saline-perfused gland and the blood-perfused pancreas in situ. 6. At high rates of secretion the PCO2 of the pancreatic juice was always higher than that of either the arterial inflow or the venous outflow. There is therefore no gradient for the passive movement of carbon dioxide between the arterial inflow and the pancreatic juice. 7. Inhibition of secretion with acetazolamide caused a fall in the PCO2 of pancreatic juice and increased the output of lactate. The secretion of lactate was not due to hypoxia as it also occurred in the blood-perfused gland in situ which had normal haemoglobin concentrations and oxygen saturation. 8. It is concluded that the secretion of bicarbonate is independent of arterial pH but critically dependent upon the arterial concentration of the bicarbonate ion. These experiments do not support the concept that the secretion of protons over the basolateral membrane is the major primary event in pancreatic secretion of bicarbonate.
Subject(s)
Arteries/physiology , Bicarbonates/metabolism , Pancreas/metabolism , Acetazolamide/pharmacology , Animals , Cats , Hydrogen-Ion Concentration , In Vitro Techniques , Pancreas/drug effects , Pancreatic Juice/metabolismABSTRACT
Groups of up to 13 pregnant rats were individually caged. Body weight, food and water consumption were recorded at days 1, 8, 15 and 22 of gestation and the dams were treated on days 8-15 with sodium chlorite, 0.1%, 0.5% or 2% in drinking water or by injection of 10, 20, or 50 mg/kg IP or by gavaging with 200 mg/kg. To prevent ingestion of stillborn pups some dams were sacrificed at day 22. Other dams were allowed to deliver at term. Fetuses were weighed, measured and examined for soft tissue and skeletal malformations. Sodium chlorite, 20 or 50 mg/kg daily IP or gavaging with 200 mg/kg, caused vaginal and urethral bleeding. Doses of 10, 20 or 50 mg/kg daily IP caused 0, 50 and 100% mortality of dams, respectively. No deaths were caused by sodium chlorite in the drinking water, but the dams' body weight, water and food consumption decreased during all treatments except 0.1% in the drinking water. Blood smears from the dams injected IP or drinking 2% sodium chlorite showed irregular, bizarre and ruptured erythrocytes. Injection of 10 or 20 mg/kg or drinking 2% resulted in decreased litter size and increased stillbirths and resorption sites. Drinking 0.1% or 0.5% sodium chlorite did not produce any significant embryotoxicity. With all treatments, no significant gross soft tissue or skeletal malformations were observed. Postnatal growth of the pups was not affected by any treatment of the dams during the gestation period.
Subject(s)
Chlorides/toxicity , Fetus/drug effects , Teratogens , Administration, Oral , Animals , Body Weight/drug effects , Chlorides/administration & dosage , Dose-Response Relationship, Drug , Erythrocytes/drug effects , Female , Injections, Intraperitoneal , Maternal-Fetal Exchange , Pregnancy , Rats , Rats, Inbred StrainsABSTRACT
The acute intracerebroventricular administration of sodium selenite and selenomethionine in conscious mice produced neurotoxicity manifested by hyperreflexia, convulsions and dealth. Selenite was 43-fold more toxic than selenomethionine on the basis of LD50 determination. The intravenous administration of the selenium compounds resulted in predominantly cardio-respiratory effects, hind limb paralysis and death. Selenite was 4-fold more toxic than selenomethionine. A comparison of relative toxicity after icv or iv administration revealed that selenite is more toxic than selenomethionine and greater relative toxicity was noted via the icv route. This toxicity difference may be attributed to the lack or low level of biotransformation of selenite by the CNS.
Subject(s)
Selenium/toxicity , Selenomethionine/toxicity , Animals , Behavior, Animal/drug effects , Female , Injections, Intravenous , Injections, Intraventricular , Male , Mice , Nervous System Diseases/chemically induced , Selenious Acid , Selenium/administration & dosage , Selenomethionine/administration & dosageSubject(s)
Cations, Divalent , Cations, Monovalent , Electrocardiography , Nervous System/drug effects , Animals , Cations, Divalent/administration & dosage , Cations, Divalent/pharmacology , Cations, Monovalent/administration & dosage , Cations, Monovalent/pharmacology , Female , Injections, Intraventricular , Male , Muscle Tonus/drug effects , Rabbits , Seizures/chemically inducedABSTRACT
Investigating the effects of Li and Rb on the toxicity of digoxin and ouabain revealed Li to be a potentiator while Rb to be a protector. The effects of Rb in this respect are, more or less, qualitatively comparable to those of K; the intensity of Rb effects is more than that of K. In case of digoxin the effect produced from the combined use of both Rb and K is more than each individual effect. With ouabain, however, whereas Rb offered protection K failed to do so. Electrolyte changes in cardiac tissue showed that Li increased the tissue content of Ca while Rb produced the opposite effect. In comparing Rb with K, both increased the K level in the cardiac muscle. However, in the case of ouabain the infusion of K failed to decrease the Ca level and this might explain its failure to protect against ouabain toxicity. This points to the importance of Ca, rather than K, in controlling the excitability of the cardiac muscle and in effecting the toxicity of cardiac glycosides. Evidences presented indicate the superiority of Rb over K and propose its trial in clinical practice.
Subject(s)
Digoxin/toxicity , Lithium/pharmacology , Rubidium/pharmacology , Animals , Digitalis Glycosides/blood , Digoxin/antagonists & inhibitors , Drug Synergism , Electrolytes/metabolism , Female , Guinea Pigs , Lethal Dose 50 , Male , Myocardium/metabolism , Ouabain/toxicity , Potassium/pharmacologyABSTRACT
When studying some of the properties of 5-hydroxytryptamine (5HT) receptors in the rat uterine muscle using phenoxybenzamine (PBZ) as an antagonist it was found that the specific receptors for 5HT in the smooth muscle were selectively blocked by PBZ; a period of 20-minute exposure to the antagonist was required for maximal effect. The blockade produced was of long duration and the recovery of response was relatively slow; it was incomplete throughout the 4-hour observation period. A concentration of 1 X 10(-8) g/ml PBZ produced a parallel shift of the dose-response effects while higher concentrations reduced both the slope and maximal response. The reasons for such a shift were discussed. 5HT produced a rapid onset and offset of effect suggesting that the site of 5HT receptor is on the surface of the cell membrane. Moreover, 5HT could protect its own receptor against PBZ blockade.