Determination of G and P genotypes of bovine group A rotavirus with emergence of unusual G- and P-type combinations from neonatal calf diarrhea in Kashmir, India.

A total of 490 diarrhoeic samples from calves aged between 0 and 6 months were screened for the presence of different G- and P-genotypes of rotavirus circulating in bovines in the Kashmir Valley. Of the 490 diarrhoeic samples, Group A rotavirus was detected in 68 (13.87%) samples by polymerase chain reaction (PCR) followed by RNA-PAGE. Genotyping analysis revealed G10, G6, G3, P[11] and P[5] to be the predominant types. The most common types of combinations detected were G10P[11] (27.90%) and G6P[11] (20.60%). The prevalence rate of G10 and P[11] decreased from 60% to 36.76% and 100%-69.11%, respectively. Genotypes G6, G3, P[1] and P[5], which were not previously reported, were detected and unusual combinations such as G6P[11], G3P[11], G10P[5], G3P[5], G6P[1], G6P[5], G6+G8P[11] were also observed for the first time. Fluctuations in the predominant types, emergence of new types and possible genetic reassortment events suggest an unstable epidemiological situation and the need for continuous surveillance of the circulating types to ensure the suitability of the vaccination programme. The present data suggests G10, G6, P[11] and P[5] genotypes could be incorporated in the polyvalent vaccine to offer increased protection against bovine rotavirus infection in India.

Evidence of novel Treponema phylotypes implicated in contagious ovine digital dermatitis and association of treponemes with major lameness causing foot pathogens.

In this study 269 swabs collected from 254 ovine foot lesions and 15 apparently healthy ovine feet were screened by PCR for the presence of major lameness causing foot pathogens viz. Treponema species, D. nodosus, F. necrophorum and T. pyogenes with the presumption that ovine foot lesion positive for Treponema species alone or in association with other three pathogens were categorized as contagious ovine digital dermatitis (CODD). While samples positive for D. nodosus alone or its combination with F. necrophorum and T. pyogenes were considered as footrot (FR) and samples in which F. necrophorum or T. pyogenes was found either alone or in combination were considered as interdigital dermatitis (ID). The overall occurrence of Treponema sp. in ovine foot lesions was 48.0%, and ranged from 33 to 58%. In Treponema positive samples D. nodosus, F. necrophorum and T. pyogenes were present in 34 (27.4%), 66 (54.4%) and 84 (68.5%) in contrast to Treponema negative samples in which these were present in 15 (11.1%), 20 (14.12%) and 17 (12.6%) samples, respectively. The data signifies that Treponema sp. are significantly associated with these foot pathogens and their different combinations with Treponema sp. influence the severity of CODD lesion. The identification of Treponema phylotypes was done by sequencing the 16S rRNA gene fragment of ten representative samples. Out of ten sequences, four (Trep-2, Trep-4, Trep-7 and Trep-10) were identical to Treponema sp. phylotype 1 (PT1) that belongs to phylogroup T. refringens-like, one sequence (Trep-1) was genetically close (90% sequence homology) to Treponema brennaborense while five sequences (Trep-3, Trep-5, Trep-6, Trep-8 and Trep-9) matched with uncultured bacterium clones of treponemes forming separate monophyletic group in phylogenetic tree and could represent new digital dermatitis phylogroup presently containing five ovine specific phylotypes. This is the first report on the presence of Treponema phylotypes other than three digital dermatitis (DD) Treponema phylogroups viz. T. phagedenis-like, T. medium/T. vincentii-like, and T. pedis-like that are frequently detected in CODD lesions. Metagenomic analysis of two representative samples revealed the abundance of genus Treponema in CODD lesion while this genus was absent in swab collected from clinically healthy foot suggesting that it might play primary role in producing CODD. These findings may further aid in understanding the etiopathogenesis of CODD and could help to develop appropriate treatment and mitigation strategies to combat the disease.

Sagittal sinus thrombosis in a patient with familial Protein C deficiency: Highlighting the impact of thrombophilia testing.

Plasma protein-C is a natural anticoagulant that inactivates factors Va and VIIIa. Familial protein C deficiency is inherited as an autosomal dominant disorder. The homozygous or compound heterozygous type may present early as purpura fulminant, while the heterozygous type can present as thromboembolism later in life. Presented in this report is a case of a 21-year-old female patient with protein-C deficiency, confirmed by thrombophilia investigations. She experienced recurrent deep vein thrombosis and cerebral sinus thrombosis due to thrombotic occlusion. She had a family history of deep vein thrombosis. Hence, high-risk cases should be seriously considered for long term anticoagulation therapy. The utility versus futility of thrombophilia testing in a particular situation is discussed to address and ensure safe practice among patients with thromboembolism.

Propidium monoazide conventional PCR and DNA sequencing: detection of negative culture bacterial pathogens causing subclinical mastitis.

AIMS: This study was conducted to early detect the negative culture bacterial pathogens causing subclinical mastitis for the fast diagnosis of the disease and the reduction of some milk-transmitted pathogenic bacteria to human consumers. METHODS AND RESULTS: A total of 171 positive California mastitis test (CMT) milk samples collected from asymptomatic dairy cows in Sharkia Governorate, Egypt were examined by conventional bacteriological methods. The obtained results revealed that Streptococcus species (77·2%), followed by Staphylococcus species (48·6%) and Escherichia coli (25·7%) were the most predominant bacterial pathogens isolated from positive culture milk samples, whereas Enterobacter and Pseudomonas species were the lowest ones (1·2%, for each). Herein, 13 (7.6%) negative culture milk samples were subjected to propidium monoazide (PMA) conventional PCR assay, followed by DNA sequencing of purified PCR amplicons. Sequence analysis identified seven different types of negative culture bacterial pathogens comprising as following; 4 Enterococcus hirae, 2 Bacillus cereus, 2 Staphylococcus aureus, 1 Bacillus mycoides, 1 Bacillus subtilis, 1 Enterococcus faecium and 1 Escherichia coli. CONCLUSIONS: All the detected negative culture bacterial pathogens by PMA-PCR assay, followed by DNA sequencing were incriminated in causing subclinical mastitis disease and had serious implications on human public health through consumption of milk contaminated with those recovered bacterial pathogens. SIGNIFICANCE AND IMPACT OF THE STUDY: The used methods could be useful in the routine detection of negative culture bacterial pathogens present in milk and consequently, it will help in the rapid diagnosis of subclinical mastitis disease and the reduction of many milk-transmitted diseases to human.

Epidemiology, spectrum of clinical manifestations and diagnostic issue of acquired haemophilia: A case series.

INTRODUCTION: Acquired haemophilia A (AHA) is a rare acquired bleeding disorder caused by polyclonal immunoglobulin G autoantibodies against clotting factor VIII (FVIII). The incidence was reported to be rare occurring in 0.2- 4 cases/million/year. Patients may present with different clinical manifestations to various specialties. Early recognition of the disease contributes to favourable clinical outcome. CASE SERIES: Here, we reported five cases of this disorder with different clinical presentations from two tertiary hospitals in Kelantan state, Malaysia within a two year-period. Most of them were elderly, except for one who presented at the age of 36 years old. No direct or secondary cause was identified except for one patient who had developed from pregnancy-related at 3 weeks postpartum. These patients presented with spontaneous bleeding typically into skin, muscles, and mucous membranes but also at rare site in the epidural space. All patients denied previous history of bleeding or family history of bleeding disorder. FVIII activities were recorded between <1% to 19%, while the inhibitor titre levels were between 3.9 BU to 340 BU. The treatment approaches especially at presentation were complicated by unfamiliarity of managing this rare condition but all these patients received appropriate medical attention. DISCUSSION: Prompt diagnosis and management in the right hand are critical. Awareness of this disorder by medical personnel at all levels in the community and in various specialties is important.

The detection and prevalence of leukotoxin gene variant strains of Fusobacterium necrophorum in footrot lesions of sheep in Kashmir, India.

The objective of this study was to determine the prevalence and identification of leukotoxin gene, lktA, variant strains of Fusobacterium necrophorum in the footrot lesions of sheep. The detection of F. necrophorum was carried out by PCR targeting the lktA gene fragment and identification of lktA variant strains was done by PCR-single stranded conformational polymorphism (PCR-SSCP) and gene sequencing. Of the 450 swabs collected from footrot lesions of sheep, 117 were lktA-positive for F. necrophorum. Of the 50 swabs collected from apparently asymptomatic sheep, only one was lktA-positive for F. necrophorum. The overall prevalence of F. necrophorum in footrot affected sheep in Kashmir valley was 26%, and ranged from 20 to 34.8%, respectively. PCR-SSCP of lktA gene fragment analysis revealed three lktA variants, designated as JKS-F1/F2/F3, while two samples (1.7%) showed multiple lktA variant strains of F. necrophorum in a single footrot-affected sheep hoof. This appears to be the first report on the presence of more than one lktA variant of F. necrophorum in a footrot lesion of sheep. The JKS-F3 lktA variant was the most frequent (75.4%), followed by JKS-F2 (14.4%) and JKS-F1 (8.4%), respectively. Among the three lktA variants identified, JKS-F3 was detected in 74 (86.0%) samples from severe footrot affected sheep with a lesion score of 4. The data suggest that JKS-F3 is the predominant lktA variant of F. necrophorum and is associated with severe footrot in sheep. Hence, JKS-F3 may be a significant variant contributing to the severity and duration of the disease in sheep.

What drives intentional overdose with non-prescription drugs? A cross-sectional study.

BACKGROUND: Use of overdosage of Non-Prescription Drugs (NPD) among university students is a serious public health issue. However, there are no extensive studies that measured the prevalence of taking more than the recommended dose of NPD and/or identified the risk associated with this behavior among university students. OBJECTIVES: This study was undertaken to assess the prevalence and associated risks of self-overdosage with NPDs in university students in United Arab Emirates (UAE). METHODS: A cross-sectional survey-based study was conducted from January to April 2014, among 2875 students in three randomly selected universities. A structured and validated questionnaire was used to collect the responses of the students. SPSS version 20 was used to analyze the data. RESULTS: Out of 2875 students, only 2355 surveys were fully answered, returned back and included in the present study. Of 2355, more than half (1348; 57.2%) the participants reported using Oral NPD (ONPD) in the past 90 days before conducting the study and were asked to complete the survey. Only 290 (22%) of a total 1348 participants reported taking more than the recommended dose of ONPD in the previous three months before conducting the study. Analgesic/antipyretic (223, 16.5%) and anti-allergic (67, 4.9%) drugs were more than other classes of the ONPD, reported to be taken in a dose, more than the recommended dosage. The most common justifications for taking more than the recommended dose of ONPD among respondents were severe symptoms (6%), the belief that the recommended dose would not be sufficient to relieve the symptom (5%), the belief that a stronger dose would relieve the symptoms faster (11%), and previous experience (4%). Our results identified three risk factors for taking more than the recommended dose of NPD. High frequently drug-users of daily use (OR=3.494, 95% CI: 1.677-7.279) (P<0.001), and students from non-medical colleges had higher odds of taking more than the recommended dosage as compared to students from medical colleges (OR=1.486, 95% CI: 1.060-2.085, P-value<0.05). Furthermore\re, participants with a poly-pharmacy behavior had higher odds of taking overdosage of ONPD than single NPD users (OR=1.918, 95% CI: 1.440-2.555) (P<0.001). CONCLUSION: There are a sizable proportion of university students that use overdosage of NPD, but it is more serious issue when it comes to non-medical student. There is a need for educational programs designed to increase awareness among all university students and to motivate them not to use overdosage of NPD. Further studies are also required to investigate additional explanatory variables that could influence the practice of overdosage with NPD.

Familial antithrombin III deficiency in a Malay patient with massive thrombosis.

Patients with low antithrombin III (AT III) has increased risk for arteriovenous thromboembolic (TE) disease. We report a 28-year-old Malay lady who presented with spontaneous right calf pain and swelling of one week duration. She was on oral contraceptive pills and had a history of travelling for a long distance prior to the presentation. Her brother who was diagnosed with AT III deficiency had arterial thrombosis at a young age. She was diagnosed as having right popliteal vein thrombosis by ultrasound and treated with subcutaneous fondaparinux. While on treatment, she developed massive bilateral pulmonary embolism (PE). Thrombophilia study showed reduced AT III activity (38µl/dl) and normal results for protein C, protein S, activated protein C resistance and lupus anticoagulant assays. This patient has heterozygous AT III deficiency added with significant acquired factors responsible for the TE events. Those with AT III deficiency may have resistance to heparin therapy and require higher doses of heparin.

Factors influencing post-cryopreserved CD34+ cells viability in the harvested products of autologous haematopoietic stem cells.

The cryopreservation process of stem cells potentially cause the loss of CD34+ cells. The aim of this study is to evaluate association of patient, graft and technical characteristics with post cryopreserved CD34+ cells viability among lymphoproliferative disease namely multiple myeloma (MM) and lymphoma patients at Hospital Universiti Sains Malaysia (USM). This retrospective study was conducted in the Transplant Unit. A search of the hospital data (2008-2018) to identify 132 patients for both MM and lymphoma who underwent autologous peripheral blood haematopoietic stem cells (APBSC) mobilisation, and were successfully harvested and cryopreserved. Selected patients' profile as well as selected parameters of stem cell mobilization and cryopreservation were obtained from laboratory information system (LIS), record unit and the Transplant Unit. Multiple logistic regression (MLR) was used to find significant associated factors and P<0.05 was considered significant. The mean age of the patients was 39 years old with almost equal gender distribution and majority were lymphoma patients, 96 (72.7%) while 36 (27.3%) were multiple myeloma (MM) patients. The significant influencing factors of post-cryopreserved CD34+ cells viability were pre-cryopreserved CD34+ cell viability, total nucleated cells (TNC), and anti-platelet and antibiotics usage. Patients who are not on anti-platelet and have higher pre-cryopreserved CD34+ cells viability have higher chance for good post-cryopreserved CD34+ cells viability. While, those patients with higher TNC and on antibiotics have lower chance for good post cryopreserved CD34+ cells viability. This study showed patients who are not on anti-platelet and antibiotics will have higher probability of achieving good post cryopreserved CD34+ cells viability. The APBSC products with higher pre-cryopreserved CD34+ cells viability and lower TNC will achieve better post-cryopreserved CD34+ cells viability. The addition of extra plasma to the APBSC products is recommended to reduce the TNC.

Interactive effects of hydrogen sulphide and silicon enhance drought and heat tolerance by modulating hormones, antioxidant defence enzymes and redox status in barley (Hordeum vulgare L.).

Recent changes in climate have reduced crop productivity throughout much of the world. Drought and heat stress, particularly in arid and semi-arid regions, have seriously affected barley production. This study explored the separate and interactive effects of silicon (Si) and hydrogen sulphide (H2 S) on plant growth and mitigation of the adverse effects of heat stress (DS) and drought stress (HS) in a barley pot experiment. The impacts of simultaneous DS + HS were more severe than individual stresses due to increased ROS production, malondialdehyde (MDA) content and higher electrolyte leakage (EL), thereby leading to reduced water, protein and photosynthetic pigment content. Exogenously applied Si and H2 S alleviated the DS-, HS- and DS + HS-induced effects on barley by reducing ROS production, MDA and EL. A single application of H2 S or Si + H2 S increased plant biomass under all stress conditions, which can be ascribed to higher Si accumulation in barley shoots. A single application of Si or H2 S significantly increased plant biomass. However, Si + H2 S was the most effective treatment for metabolite accumulation and elevating activity of antioxidant enzymes to prevent toxicity from oxidative stress. This treatment also modulated osmolyte content, enhanced antioxidant activity and regulated the stress signalling-related endogenous hormones, abscisic acid (ABA) and indole acetic acid (IAA). Exogenous treatments regulated endogenous H2 S and Si and resulted in higher tolerance to individual and combined drought and heat stress in barley.

COVID 19 in Children: Gastrointestinal, Hepatobiliary and Pancreatic Manifestation.

The most devastating pandemic of this era coronavirus disease-2019 (COVID-19) is caused by a novel virus named severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Although it is primarily a respiratory pathogen, it can also result in several extra-pulmonary manifestations includes gastrointestinal symptoms, hepatocellular injury. Angiotensin-converting enzyme-2 (ACE-2) receptor and transmembrane serine protease 2 (TMPRSS2), the entry receptor for the causative coronavirus SARS-CoV-2 is co-express in the gastrointestinal tract, hepatocyte, and cholangiocytes similar to the respiratory mucosa. The presence of these receptors facilitates the entry into the tissue and causes direct viral tissue damage, which is a proposed mechanism of injury. Diarrhoea, nausea, vomiting, abdominal discomfort are common gastrointestinal manifestations, whereas derangement of liver function tests is the most hepatic manifestation in COVID-19. In this article, we reviewed on SARS-CoV-2 disease COVID-19 regarding gastrointestinal, hepatic, and pancreatic manifestation, the mechanisms by which the virus may inflict damage, and their management perspective.

Gastrointestinal parasitic infections of buffaloes (Bubalus bubalis) in Sarawak Borneo: Prevalence, risk factors, and farming practices.

The objectives of this study were to investigate the prevalence and associated risk factors for gastrointestinal (GI) parasites in buffaloes from various areas of Sarawak, and to assess current management practices of GI parasites among farmers. Faecal samples were collected from 15 farms and 129 animals, as well as data on farm and animal-based characteristics. A total of 129 faecal samples were examined for GI parasites using a modified McMaster and sedimentation. Association between potential risk factors and the prevalence of GI parasites was investigated using Chi-square statistic. The prevalence of Paramphistomum sp., strongyles, and coccidia were 75.2% (95% CI±7.5), 52.7% (95% CI±8.6) and 48.1% (95% CI±8.6), respectively. Farms which had a grazing area less than 50 acres in size had significantly higher prevalence of strongyles (70.5%, χ2 = 8.34, P = 0.004) and paramphistomes (88.6%, χ2 = 6.46, P = 0.01) relative to farms with a larger grazing area (43.5% and 68.2%, respectively). Prevalence of strongyles was lower in farms that did not implement a cut- and-carry system (45.6%, χ2 = 4.17, P = 0.04) in comparison to those that did (64%). The prevalence of paramphistomes was higher on farms with more than 40 animals (80.6%, χ2 = 3.18, P = 0.05) relative to farms with fewer animals. The majority of farmers surveyed (67.9%) showed awareness of GI parasite infection and reported that they recognized the associated symptoms. Most farmers practised deworming, and ivermectin was the most commonly used anthelminthic (60.4%); only 1.9% of farmers used albendazole. Overall this study revealed a high prevalence of GI parasites in buffalo in Sarawak. Although farmers report they are aware of parasitic diseases, further education is still required. This could include how they can successfully implement on-farm changes to reduce the prevalence of GI parasites in their herds.

Are Dropped Bone Grafts Safe to be Re-used? - An Experimental Study Comparing Efficacy of Chlorhexidine, Povidone-Iodine and Alcohol.

INTRODUCTION: A dilemma arises when a bone graft or fracture fragment is accidentally dropped on the operation theatre floor and becomes contaminated. This study aimed to determine the efficacy of simple and readily available antiseptic solutions in disinfecting contaminated bones. MATERIAL AND METHODS: This experimental study involved 225 bone specimens prepared from discarded bone fragments during a series of 45 knee and hip arthroplasty surgeries. The bone fragments were cut into five identical cubes and were randomly assigned to either control (positive or negative), or experimental groups (0.5% chlorhexidine, 10% povidone-iodine or 70% alcohol). The control negative was to determine pre-contamination culture. All bone specimens, except the control negative group were uniformly contaminated by dropping on the operation theatre floor. Subsequently, the dropped bone specimens except for the control positive group, were disinfected by immersing in a respective antiseptic solution for 10 minutes, before transported to the microbiology laboratory for incubation. RESULTS: The incidence of a positive culture from a dropped bone fragment was 86.5%. From the 37 specimens sent for each group, the incidence of positive culture was 5.4% (2 specimens) after being disinfected using chlorhexidine, 67.6% (25 specimens) using povidone-iodine and 81.1% (30 specimens) using alcohol. Simple logistic regression analysis demonstrated that chlorhexidine was significantly effective in disinfecting contaminated bones (p-value <0.001, odd ratio 0.009). Povidone-iodine and alcohol were not statistically significant (p-value 0.059 and 0.53, respectively). Organisms identified were Bacillus species and coagulase negative Staphylococcus. No gram-negative bacteria were isolated. CONCLUSION: A total of 0.5% chlorhexidine is effective and superior in disinfecting contaminated bones.

The Relationship amongst Intervertebral Disc Vertical Diameter, Lateral Foramen Diameter and Nerve Root Impingement in Lumbar Vertebra.

Introduction: The vertical diameter of the foramen is dependent upon the vertical diameter of the corresponding intervertebral disc. A decrease in disc vertical diameter has direct anatomic consequences to the foraminal diameter and area available for the nerve root passing through it. This study is to establish the relationship amongst the intervertebral disc vertical diameter, lateral foramen diameters and nerve root compression in the lumbar vertebra. Materials and Methods: Measurements of the study parameters were performed using sagittal MRI images. The parameters studied were: intervertebral disc vertical diameter (DVD), foraminal vertical diameter (FVD), foraminal transverse diameter (FTD) and nerve root diameter (NRD) of both sides. The relationship between the measured parameters were then analyzed. Results: A total of 62 MRI images were available for this study. Statistical analysis showed moderate to strong correlation between DVD and FVD at all the lumbar levels except at left L23 and L5S1 and right L3L4 and L4L5. Correlation between DVD and FTD were not significant at all lumbar levels. Regression analysis showed that a decrease of 1mm of DVD was associated with 1.3, 1.7, 3.3, 3.3 and 1.3mm reduction of FVD at L1L2, L2L3, L3L4, L4L5 and L5S1 respectively. Conclusion: Reduction of DVD was associated with reduction of FVD. However, FVD was relatively wide for the nerve root even with complete loss of DVD. FTD was much narrower than the FVD making it more likely to cause nerve root compression at the exit foramina. These anatomical details should be given consideration in treating patients with lateral canal stenosis.

Precision, accuracy, and reliability of hemoglobin assessment with use of capillary blood.

BACKGROUND: Previous research has suggested that there may be significant within-subject variability, both site-to-site and over time, in hemoglobin concentrations in capillary blood. OBJECTIVE: This study examined the reliability of the portable hemoglobinometer (PHM) system with use of capillary blood and the implications of errors of the magnitude found for the classification of anemia status in individuals and population groups. The precision and accuracy of the method with use of venous blood were also tested. DESIGN: Three empirical data sets were used to measure reliability, precision, and accuracy of the PHM system [2 from Honduras (n = 87 and 141); 1 from Bangladesh (n = 73)]. Simulation data were used to assess the implications of errors for screening individuals for anemia and to estimate anemia prevalence. RESULTS: High within-subject variability (unreliability) was identified when capillary blood from the left hand was compared with that from the right hand (CV: 6.3%) and when measurements were taken on 4 consecutive days (CV: 7.0%). Reliability was only 69% and 50%, respectively. Precision and accuracy, however, were very high (concordance coefficients of 0.99 and 0.98 and CV < 1%). CONCLUSIONS: The simulation data showed that errors of the magnitude found due to unreliability can lead to misclassification of anemia status in individuals and small biases in anemia prevalence estimates. We recommend replicate sampling to reduce the influence of unreliability in the use of the PHM system with capillary blood.

Dopamine receptors in Parkinson's disease.

1. Parkinson's disease is associated with profound decreases in striatal dopamine concentrations. 2. There are significant increases in the densities of striatal D1 and D2 receptors as part of the compensatory mechanism. 3. Levodopa therapy induces a down-regulation of both D1 and D2 receptors to normal densities. 4. Positron emission tomography detects striatal changes in early Parkinson's disease or toxin-induced parkinsonism.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), its metabolite cyperquat (MPP+) and energy transduction in mitochondria from rat striatum and liver.

In vitro studies with rat striatal and liver mitochondria have shown that the neurotoxic compound MPTP (0.5 mM) has very little effect on mitochondrial energy transduction. With pyruvate-malate (P/M), mitochondria from striatum and liver exhibited state 3 oxygen consumption rates of 101.5 +/- 21.3 and 53.6 +/- 14.8, respectively. On the other hand, MPP+ (0.5 mM) inhibited the NAD-linked substrate (P/M) oxidation in both tissue preparations. MPP+ failed to influence oxidative phosphorylation when succinate was used as the substrate. Mitochondria from liver and striatum exhibited low levels of 45Ca uptake in the absence of Mg.ADP. This was increased by about 3-fold in the presence of Mg.ADP. MPP+ under either condition had very little effect on 45Ca uptake by these organelles.

Prevention of progression of Parkinson's disease with antioxidative therapy.

1. Oxidative mechanisms in dopaminergic neurons may contribute to cell death and the progression of Parkinson's Disease. 2. The free radical auto-toxicity concept has scientific evidence to support it. 3. Clinical trials are underway to assess the protective effect of augmenting the free radical scavenging system with vitamin E and inhibiting catecholamine oxidation with deprenyl.

Effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), cyperquat (MPP+) and paraquat on isolated mitochondria from rat striatum, cortex and liver.

The effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), its metabolite 1-methyl-4-phenyl pyridinium ion (MPP+, cyperquat) and a structurally-related compound paraquat on mitochondrial functions were investigated in isolated organelles from rat striatum, cortex and liver. MPTP (0.1-1.0 mM) had no significant effect on various parameters of mitochondrial oxidative phosphorylation. In contrast, MPP+ (0.5 mM) inhibited the oxidation of the nicotinamide adenine dinucleotide (NAD+)-linked substrates pyruvate and malate but not that of the flavin adenine dinucleotide (FAD+)-linked substrate succinate. Paraquat (5.0 mM) significantly stimulated basal oxygen consumption (state 4) without influencing the oxygen utilization (state 3) associated with adenosine diphosphate (ADP) phosphorylation. Thus, these structurally-related compounds have different effects on mitochondrial oxidative phosphorylation, but the organelles from striatum, cortex and liver were affected in a similar manner by these compounds.

Chronic treatment with bromocriptine induces behavioral supersensitivity in rats.

Chronic treatment of rotating rats with equipotent doses of the dopamine (DA) agonists apomorphine (APO), 3-(3,4-dihydroxyphenyl)-1-n-propylpyrrolidine hydrobromide (DPPP) and bromocriptine (BRO) for four weeks resulted in marked differences in rotational activity following acute administration of these agonists. Whereas chronic treatment with APO and DPPP failed to produce any significant changes in agonist-induced rotational behavior, chronic BRO treatment induced a progressive increase in rotational activity up to a mean 200% increase over controls at four weeks. These findings may, in part, explain the long-term clinical efficacy of bromocriptine in patients with Parkinson's disease.