Nodal-paranodal antibodies in HIV-immune mediated radiculo-neuropathies: Clinical phenotypes and relevance.

BACKGROUND: The frequency of nodal-paranodal antibodies in HIV-infected patients with chronic immune-mediated radiculo-neuropathies (IMRN) has not been previously described. METHODS: HIV-infected patients who met the inclusion criteria for chronic IMRN were screened for immunoglobulin G (IgG) antibodies directed against nodal (neurofascin (NF)186) and paranodal (NF155, contactin-1 (CNTN1) and contactin-associated protein(Caspr1)) cell adhesion molecules, using a live, cell-based assay. To explore potential pathogenicity, binding of human IgG to myelinated co-cultures was assessed by incubation with patients' sera positive for nodal or paranodal antibodies. Normal human serum was added as a source of complement to assess for complement activation as a mechanism for myelin injury. RESULTS: Twenty-four HIV-infected patients with IMRN were included in the study, 15 with chronic inflammatory demyelinating polyneuropathy (CIDP), 4 with ventral root radiculopathies (VRR), and 5 with dorsal root ganglionopathies (DRG). Five patients with CIDP had combined central and peripheral demyelination (CCPD). Three patients (12.7%) tested positive for neurofascin IgG1 antibodies in the following categories: 1 patient with VRR was NF186 positive, and 2 patients were NF155 positive with DRG and mixed sensory-motor demyelinating neuropathy with optic neuritis, respectively. CONCLUSION: The frequency of nodal-paranodal antibodies is similar among IMRN regardless of HIV status. Interpretation of the results in the context of HIV is challenging as there is uncertainty regarding pathogenicity of the antibodies, especially at low titres. Larger prospective immune studies are required to delineate pathogenicity in the context of HIV, and to establish a panel of antibodies to predict for a particular clinical phenotype.

Improvement of rooting and growth in kiwifruit (Actinidia deliciosa) cuttings with organic biostimulants.

Seaweed extracts have shown profoundly positive effects on crop growth, quality and reproduction in diverse agricultural and horticultural crops. Seaweed extracts can be used to promote the rooting and growth of cuttings in perennial fruit species like kiwifruit (Actinidia deliciosa). In this study, the cuttings were treated with 1, 5, 10 and 50% solutions of G Sap (Gracilaria edulis), K Sap (Kappaphycus alvarezii), AN (Ascophyllum nodosum), EM (Ecklonia maxima), HA (Humic acid) and control (water) for 6 h as base dipping. Subsequently, the treatments of G Sap, K Sap, AN, EM, HA and control were repeated every 15 days for a period of six months as application of 50 ml solutions in the potted cuttings. All the treatments exhibited significant effects on the rooting percent in all the kiwifruit cultivars, namely 'Monty', 'Abott', 'Hayward', 'Allison' and 'Bruno' (P ≤ 0.01) as compared to the control. Shoot and root growth parameters including leaf number per cutting, number of roots per cutting, number of branches, plant height, shoot diameter, root length, root diameter and root weight were all positively increased with the application of seaweed extracts (P ≤ 0.05). Cuttings treated with seaweed extract exhibited significantly higher levels of pigments (chlorophyll a, chlorophyll b and total carotenoids), metabolites (total carbohydrates and soluble phenols) and less electrolyte leakage as compared to the control cuttings. Significant positive and negative correlations were observed between biochemical parameters combined with plant nutrient concentration. Principal component analysis (PCA) revealed that PC1 and PC2 (first two principal components) accounted for 75% of the entire variation. While, PC1 accounted for 63% of the total variation, PC2 accounted for 11% of the total variation. The leaves and the roots of kiwifruit cultivar 'Hayward' treated with G Sap at 10%, K Sap at 10%, AN at 10%, EM at 10%, HA at 10% exhibited higher expression of all four root promoting candidate genes (GH3-3, LBD16, LBD29 and LRP1) compared to the control. Therefore, it can be concluded that, seaweed extract and humic acid can be used as a suitable alternative to synthetic hormones for promoting the rooting and growth of kiwifruit cuttings.

Unraveling the pathways influencing the berry color and firmness of grapevine cv. Flame Seedless treated with bioregulators using biochemical and RNA-Seq analysis under semi-arid subtropics.

Plant bioregulators (PBRs) regulate developmental and physiological processes in plants. In this study, biochemical and transcriptomic analyses were conducted to evaluate the influence of PBRs [abscisic acid (ABA), benzothiadiazole (BTH), ethephon, and prohexadione-calcium (Pro-Ca)] on the grapevine cv. Flame Seedless under semi-arid subtropics. This study aims to see the effect of exogenous application of PBRs on overall berry quality, including uniformity of berry color. Uniform colored berries, the maximum total soluble solids (TSS) and total antioxidant activity (TAoA), and the highest total phenolics (TPC) and flavonoids (TFC) contents were obtained with the treatments, namely, 400 mg L-1 ethephon and 400 mg L-1 ABA. Further, RNA-Seq analysis has also identified some key DEGs like UFGT (VIT_16s0039g02230), GST (VIT_04s0079g00690), and chalcone synthase (CHS) (VIT_05s0136g00260) which were part of the anthocyanin biosynthesis pathway controlling grape berries color. Thus, ethephon (400 mg L-1) and ABA (400 mg L-1) were found promising for attaining greater uniformity in berry color development because of increased total anthocyanins content. In addition, they were also found associated with enhanced TAoA, TPC, and TFC. Hence, ethephon and ABA can be recommended for improving the berry quality.

Stability-indicating HPLC Method for Simultaneous Determination of Aspirin and Prasugrel.

A simple, sensitive, specific, accurate, and stability-indicating reversed phase high performance liquid chromatographic method was developed for the simultaneous determination of aspirin and prasugrel, using a Kromasil 100 C18 (150×4.6 mm, 5 µ) column and a mobile phase composed of acetonitrile:methanol:water (30:10:60, v/v), pH 3.0 adjusted with o-phosphoric acid. The retention times of aspirin and prasugrel were found to be 3.28 min and 6.61 min, respectively. Linearity was established for aspirin and prasugrel in the range of 15-150 and 2-20 µg/ml, respectively. The percentage recoveries of aspirin and prasugrel were found to be in the range of 99.34-100.32% and 98.92-102.09%, respectively. Both the drugs were subjected to acid, alkali and neutral hydrolysis, oxidation, dry heat, and UV degradation. The degradation studies indicated aspirin to be more susceptible to alkaline hydrolysis, while prasugrel to be more susceptible to neutral hydrolysis. The degradation products were well resolved from the pure drug with significant differences in their retention time values. This method can be successfully employed for simultaneous quantitative analysis of aspirin and prasugrel in bulk drugs and formulations.

Quality evaluation of co-composted wheat straw, poultry droppings and oil seed cakes.

Poultry droppings, neem cake, castor cake, jatropha cake and grass clippings were used separately as organic nitrogen additives to decrease the high C:N ratio of wheat straw. Composting was carried out aerobically in presence of fungal consortium developed by including Aspergillus awamori, Aspergillus nidulans, Trichoderma viride and Phanerochaete chrysosporium. The degraded product was characterized to assess the technical viability of organic nitrogen supplements as well as fungal consortium in improving the quality of compost and hastening the process of decomposition of high lignocellulolytic waste. Evaluation of maturity showed that mixture of wheat straw, poultry dropping and jatropha cake had the lowest C:N ratio of 10:1, the highest humic acid fraction of 3.15%, the lowest dehydrogenase activity and a germination index exceeding 80% in 60 days of decomposition. Inoculated and grass clipping amended wheat straw-poultry dropping mixture resulted in compost with highest humus content of 11.8% and C:N ratio of 13.5, humic acid fraction of 2.84% and germination index of 59.66%. Fungal consortium was effective in improving the humus content of all the composted mixtures. In some treatments, germination index could not be correlated with C:N ratio. Non edible oil seed cake supplemented substrate mixtures did not respond to fungal inoculation as far as C:N ratio was concerned.

Temporal evolution of cerebrospinal fluid following initiation of treatment for tuberculous meningitis.

OBJECTIVE: Clinicians often perform follow-up lumbar punctures (LPs) on patients with tuberculous meningitis (TBM) to document changes occurring in the cerebrospinal fluid (CSF). Normalisation of the CSF then serves as indirect confirmation of the diagnosis. However, changes occurring in CSF following the initiation of anti-tuberculosis (TB) treatment are not well described. We undertook a retrospective study to determine the temporal evolution of CSF in patients with TBM on anti-TB treatment in an attempt to provide a more rational basis for the interpretation of repeat LPs. METHODS: Patients diagnosed with TBM at King George V Hospital in Durban from 1994 to 2003 were identified. Demographic, clinical, laboratory and radiological data were recorded. We examined the change in CSF lymphocyte cell count, polymorphonuclear (PMN) cell count, glucose concentration and protein concentration. Initially, scatter plots of the data modelled over time were produced and random effects models were then used to model the predicted changes in CSF over time. RESULTS: Ninety-nine patients were identified, and a total of 327 LPs were done. The average number of LPs per patient was 3 (range 3 - 9). Statistically significant changes in all four variables (lymphocytes, PMN cells, glucose and protein) were demonstrated, with a p value < 0.001. The predicted models showed that lymphocyte count and protein concentration change slowly over time. PMN cells and glucose concentration changed rapidly in an exponential manner. CONCLUSIONS: Our results demonstrate the tendency for CSF to normalise over time. The slow change in lymphocyte count and protein concentration limits clinical use. The rapid change in PMN cells and glucose concentration allows us to make reasonable clinical decisions. If a repeat LP does not show definite improvement in these two parameters, it should be considered atypical for TBM.

Neurosyphilis: a Clinico-Radiological Study

Purpose. Neurosyphilis is an uncommon disease. Although syphilis may promote the transmission of HIV the converse may not be true. The neuro-radiology of neurosyphilis is limited to two case series and several case reports. Our series of patients were reviewed to describe the clinical and radiological findings. Method. A retrospective chart review from 1994 to 2005 was done and demographic; clinical; laboratory and radiological findings were extracted. Patients HIV status was also recorded. Patients who satisfied the criteria for the diagnosis of neurosyphilis with the exclusion of alternate diagnoses were included. Results. Fifty-three patients were evaluated but only 41 charts were available for review. Thirty-nine of these had radiological data. The clinical spectrum included asymptomatic patients; strokes; dementia; cranial nerve palsies; spinal cord syndromes and polyradiculopathy. Imaging changes included normal findings; infarcts; meningeal based mass lesions; spinal intra-medullary hyper-intensities; cranial nerve enhancement and intra-medullary enhancing mass lesions. There was no difference in CSF cellular or chemistry findings between those with neurosyphilis who were HIV positive and those who were HIV negative. Amongst the patients where follow up was available most improved regardless of HIV status. Conclusion. Neurosyphilis has protean manifestations and can affect any central neurological system. The pathogenesis varies from inflammatory mass lesions to vascular occlusion and inflammatory damage. Syphilis should be an aetiological consideration in any neurological presentation where another cause is not obvious. The radiological features are not specific and would be seen with many inflammatory aetiologies affecting the CNS. The CSF picture is similar regardless of HIV status and patients should be managed similarly regardless of their HIV status

Ischemic stroke in young HIV-positive patients in Kwazulu-Natal, South Africa.

Cerebrovascular disease occurs in HIV-positive individuals, but no relationship between the two has been established. The authors reviewed a cohort of patients aged 15 to 44 years to evaluate stroke in HIV-positive and negative subjects. Patients who were HIV-positive with no other identifiable etiology were compared to age- and race-matched HIV-negative patients. HIV-positive and HIV-negative groups did not differ in angiographic, cardiac, or serologic tests. A positive HIV test does not provide causal information or diagnosis.

Multidrug-resistant tuberculous meningitis in KwaZulu-Natal, South Africa.

Multidrug-resistant (MDR) pulmonary tuberculosis (TB) is well described in the literature. Reports of MDR TB meningitis (MDR-TBM), however, are limited to case reports and a single case series. During the period of 1999-2002, 350 patients with TBM were identified by cerebrospinal fluid culture for TB. Thirty patients (8.6%) had TB that was resistant to at least isoniazid and rifampicin. All 30 patients were included in this study. We reviewed hospital charts of the patients with MDR-TBM and describe our experience. Seventeen patients with MDR-TBM died, and, of those who were known to be alive, many experienced significant morbidity. Eighteen patients were HIV positive. Twenty-two patients had been treated for TB in the past, 3 patients had received no previous treatment for TB, and the history of TB treatment was unknown for 5 patients. The study highlights the prevalence of MDR-TBM and identifies new challenges in the management of affected patients.

Oral trimethoprim-sulfamethoxazole in the treatment of cerebral toxoplasmosis in AIDS patients--a prospective study.

Toxoplasma encephalitis is the commonest cause of intracranial mass lesions in AIDS patients. Effective therapy includes pyrimethamine plus sulfadiazine, clindamycin with pyrimethamine, and co-trimoxazole. This study examines the efficacy of oral co-trimoxazole in 20 AIDS patients with toxoplasmosis and seeks to confirm the experience of Torre et al.

Preparation and comparative clinical evaluation of liposomal gel of benzoyl peroxide for acne.

A novel topical benzovl peroxide (BP) gelformulation containing liposomal BP was shown to significantly reduce local irritation relative to its nonliposomal BP gel (plain BP gel) preparation and also to improve clinical efficacy (almost twofold) in the treatment of acne. BP liposomes were prepared, optimized, and formulated into a carbopol 934gel base. Drug release evaluated using dialysis membrane has repeatedly shown that a new topical gel formulation containing liposomal BP (liposomal BP gel) significantly reduced BP penetration. Clinical evaluation data were also compared with those obtained with liposomal tretinoin (TRE) gel in an earlier investigation of ours. The overall improvement in terms of percentage reduction in total number of skin lesions demonstrated almost similar results for both BP and TRE. However, variation was observed in the treatment of separate types of lesions in which liposomal TRE gel was found to be more effective in treating comedones and liposomal BP gel in treating papules and pustules. Also, the liposomal gel formulation of both the drugs significantly reduced the local adverse effects, thereby improving patient compliance.

Ethanol and oxidative stress.

This article represents the proceedings of a workshop at the 2000 ISBRA Meeting in Yokohama, Japan. The chair was Albert Y. Sun. The presentations were (1) Ethanol-inducible cytochrome P-4502E1 in alcoholic liver disease, by Magnus Ingelman-Sundberg and Etienne Neve; (2) Regulation of NF-kappaB by ethanol, by H. Matsumoto, Y. Nishitani, Y. Minowa, and Y. Fukui; (3) Chronic ethanol consumption increases concentration of oxidized proteins in rat liver, by Shannon M. Bailey, Vinood B. Patel, and Carol C. Cunningham; (4) Antiphospholipids antibodies and oxidized modified low-density lipoprotein in chronic alcoholic patients, by Tomas Zima, Lenka Fialova, Ludmila Mikulikova, Ptr Popov, Ivan Malbohan, Marta Janebova, and Karel Nespor; and (5) Amelioration of ethanol-induced damage by polyphenols, by Albert Y. Sun and Grace Y. Sun.

Ethanol and protein metabolism.

This article represents the proceedings of a workshop at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Carol C. Cunningham and Victor R. Preedy. The presentations were (1) Ribosomal content, ribosomal localization and the levels of ribosomal protein mRNA and rRNA in rat skeletal muscle exposed to ethanol, by Alistair G. Paice, John E. Hesketh, Timothy J. Peters, and Victor R. Preedy; (2) Altered hepatic mitochondrial ribosome structure after chronic ethanol administration, by Vinood B. Patel and Carol C. Cunningham; (3) Clinical aspects of hepatic protein metabolism and alcohol, by Elena Volpi; and (4) Effects of oral intake of alanine plus glutamine on ethanol metabolism and ethanol-related depression in motor activity, by Kazunori Mawatari, H. Masaki, M. Mori, and Kunio Torii.

C-reactive protein: a 'golden marker' for inflammation and coronary artery disease.

Numerous studies have shown that elevated levels of C-reactive protein (CRP) are associated with increased cardiovascular risk. We advocate greater use of CRP measurements in clinical practice to identify patients at high risk in a variety of situations.

Cardioprotective effect of propranolol from alcohol-induced heart muscle damage as assessed by plasma cardiac troponin-t.

BACKGROUND: Heavy alcohol consumption from either long-term misuse or binge drinking is associated with poor cardiac contractility, mitochondrial dysfunction, and ventricular arrhythmias. The aim of this study was to measure circulating cardiac troponin-T as a marker for myocardial damage following acute and chronic alcohol administration. METHODS: In acute studies, male Wistar rats were treated with alcohol (75 mmol/kg body weight, intraperitoneal) and plasma was collected 2.5 hr after alcohol administration for analysis of rat cardiac troponin-T. In addition, rats were pretreated with cyanamide (an inhibitor of acetaldehyde dehydrogenase), various beta-blockers, xanthine oxidase inhibitors, or lisinopril before acute alcohol dosing. In chronic studies, rats were fed alcohol (as 35% of total dietary calories) for 6 weeks. RESULTS: The results of the time course study showed that acute alcohol administration significantly raised plasma cardiac troponin-T levels after 2.5 hr and 6 hr, but not after 24 hr. The effects of alcohol on cardiac troponin-T were potentiated with cyanamide pretreatment. Acute ethanol, alone or with cyanamide pretreatment, decreased systolic blood pressure and increased heart rates. Beta-blocker pretreatment with propranolol reduced the alcohol-induced increase in plasma troponin-T, whereas lisinopril potentiated this effect. The beta-blockers, atenolol and metoprolol, and the xanthine oxidase inhibitors, allopurinol and oxypurinol, were unable to reduce elevated troponin-T. However, pretreatment with the beta-blocker timolol moderated the acute alcohol-induced increase in troponin-T. In the chronic alcohol rat model, no differences were observed between alcohol and control pair-fed rats, suggesting the inducement of tolerance. CONCLUSIONS: In conditions of acute exposure, ethanol-induced lesions are characterized by raised plasma cardiac troponin-T possibly due to beta1 and/or beta2 adrenergic activation.

Chronic ethanol consumption alters the glutathione/glutathione peroxidase-1 system and protein oxidation status in rat liver.

BACKGROUND: Alcohol-induced liver damage is associated with oxidative stress, which might be linked to disturbances in liver antioxidant defense mechanisms. The effect of chronic ethanol consumption on the mitochondrial and cytosolic glutathione/glutathione peroxidase-1 (GSHPx-1) system and oxidative modification of proteins was therefore studied in the rat. METHODS: Male Sprague-Dawley rats were fed liquid diets that provided 36% total calories as ethanol for at least 31 days. Pair-fed controls received isocaloric diets with ethanol calories substituted with maltose-dextrins. Mitochondrial and cytosolic fractions were prepared from livers and assayed for GSHPx-1 and glutathione reductase activities and total and oxidized concentrations of glutathione. Catalase activity was measured in the postmitochondrial supernatant. Levels of GSHPx-1, lactate dehydrogenase, and the beta subunit of the F1 portion of the ATP synthase protein were determined by western blot analysis. Concentrations of mitochondrial and cytosolic protein carbonyls were measured to assess ethanol-induced oxidation of proteins. RESULTS: Chronic ethanol consumption significantly decreased cytosolic and mitochondrial GSHPx-1 activities by 40% and 30%, respectively. Levels of GSHPx-1 protein in cytosol were unaffected by ethanol feeding, whereas there was a small decrease in GSHPx-1 protein levels in mitochondria isolated from ethanol-fed rats. Glutathione reductase activities were increased in both intracellular compartments and catalase activity was increased as a consequence of ethanol exposure. Cytosolic total glutathione was mildly decreased, whereas ethanol feeding increased mitochondrial levels of total glutathione. Chronic ethanol feeding significantly increased both cytosolic and mitochondrial concentrations of protein carbonyls by 30% and 60%, respectively. CONCLUSIONS: This study demonstrates that chronic ethanol-induced alterations in the glutathione/GSHPx-1 antioxidant system might promote oxidative modification of liver proteins, namely those of the mitochondrion, which could contribute to the adverse effects of ethanol on the liver.

Diarrhea reduces the rates of cardiac protein synthesis in myofibrillar protein fractions in rats in vivo.

Although chronic diarrhea affects heart function and morphology, the pathogenic mechanisms are unknown. It was our hypothesis that diarrhea imposes metabolic stress to inhibit the synthesis of new contractile proteins. To test this hypothesis, we investigated the effects of lactose-induced diarrhea in rats. The groups were: 1) freely fed controls, 2) rats with lactose-induced diarrhea or 3) pair-fed rats. After 1 wk, hearts from the rats were subjected to subcellular fractionation techniques to isolate the major protein fractions, including myofibrillar proteins. The rates of protein synthesis were measured with concomitant assay of cardiac composition and plasma analytes. In comparison with the control group, diarrhea induced the following changes (P < 0.05): a decrease in heart weight, reduced RNA and mixed protein contents and a reduction in the fractional rate of mixed protein synthesis. There was a reduction in the content of all protein fractions. The fractional synthesis rate was reduced only for the myofibrillar fraction. Plasma insulin-like growth factor-I, but not corticosterone, was reduced. Plasma cholesterol and triglyceride concentrations were also reduced. In comparison with the pair-fed group, diarrhea induced the following changes (P < 0.05): a reduction in heart weight and fractional rate of mixed protein synthesis, reduced myofibrillar absolute synthesis rate and increased sarcoplasmic/myofibrillar fractional synthesis rate ratio. Plasma bicarbonate, triglyceride and urea concentrations were reduced, with an increase in albumin. Diarrhea impaired cardiac biochemistry, including a reduction in protein content and synthesis. A substantial proportion of these changes is due to anorexia, but the selective reduction in the synthesis of contractile proteins is a feature exclusive to the diarrhea group and may be due to reductions in plasma insulin-like growth factor-I.

In vivo protein synthetic rates of atrial, ventricular, and pulmonary tissue proteins in aortic constriction, goldblatt, and bromoethylamine models of hypertension.

Changes in tissue protein synthesis in hypertension have usually been measured in vitro in heart from acutely hypertensive rats without consideration of changes in atrial or pulmonary tissue or changes occurring in long-standing hypertension. The objective of the study was to investigate the in vivo changes in cardiopulmonary protein synthesis in three different rat models of chronic hypertension. Hypertension in aortic constriction, the Goldblatt model, and the bromoethylamine model were induced in rats for 30 days. At the end of the experimental period, in vivo rates of protein synthesis were measured with a flooding dose of [3H]phenylalanine (a method which effectively considers precursor pools). Concomitant measurements included quantification of contractile protein and RNA and DNA contents. Indices of protein breakdown were also assessed by selective measurement of protease activities. At the end of 30 days, aortic constriction induced marked increases in protein contents of the left ventricle, septum, left atria, and lungs. Accompanying changes included concomitant increases in RNA and DNA contents. Left ventricular myofibrillary, sarcoplasmic, and stromal protein contents increased in the aortic constriction model. Less marked changes occurred in the Goldblatt model, though the left atria were not significantly affected. In contrast, the bromoethylamine model had no effect on the protein or RNA contents of any region. In all cardiac regions of all three models, fractional rates of protein synthesis were not significantly affected. However, protein synthesis increased in the lungs of both the Goldblatt and bromoethylamine models at 30 days. Protease activities were decreased in the left ventricles of all three models at 30 days, with lysosomal protease activities declining in the aortic constriction model and cytoplasmic protease activities declining in the other two models. The failure of chronic hypertension to increase ventricular synthesis rates may represent inherent limitations in the time frame for measuring protein synthesis in vivo. However, at earlier time points (i.e., 10 days), the aortic constriction model was characterized by marked increases in left ventricular and atrial protein contents, RNA contents, and fractional rates of protein synthesis. This was consistent with the supposition that, in acute phases of hypertrophy, rates of protein synthesis increase, whereas in established hypertrophy, synthesis rates remain unchanged or decrease. The applicability of the aortic constriction model was investigated by examining the effects of the angiotensin converting enzyme inhibitor lisinopril (5 mg/kg/day). After 30 days treatment, lisinopril impeded the increase in left ventricular mixed and myofibrillar proteins. This effect was accompanied by an apparent increase in protein synthesis. In conclusion, although all three chronic models are able to induce hypertension, varying degrees of hypertrophy develop, which are more pronounced in the aortic constriction model. Accompanying changes include hypertrophy in the atria, reduced rates of ventricular proteolytic activity, and altered rates of protein metabolism in the lungs.