Neurological disorders associated with COVID-19 in Sri Lanka.

BACKGROUND: Neurological manifestations of SARS-CoV-2 infection have been reported from many countries around the world, including the South Asian region. This surveillance study aimed to describe the spectrum of neurological disorders associated with COVID-19 in Sri Lanka. METHODS: COVID-19 patients manifesting neurological disorders one week prior and up to six weeks after infection were recruited from all the neurology centres of the government hospitals in Sri Lanka from May 2021 - May 2022. Data was collected using a structured data form that was electronically transmitted to a central repository. All patients were evaluated and managed by a neurologist. Data were analysed using simple descriptive analysis to characterise demographic and disease related variables, and simple comparisons and logistic regression were performed to analyse outcomes and their associations. RESULTS: One hundred and eighty-four patients with neurological manifestations associated with COVID-19 were recruited from all nine provinces in Sri Lanka. Ischaemic stroke (31%) was the commonest neurological manifestation followed by encephalopathy (13.6%), Guillain-Barre syndrome (GBS) (9.2%) and encephalitis (7.6%). Ischaemic stroke, encephalitis and encephalopathy presented within 6 days of onset of COVID-19 symptoms, whereas GBS and myelitis presented up to 10 days post onset while epilepsy and Bell palsy presented up to 20 - 40 days post onset. Haemorrhagic stroke presented either just prior to or at onset, or 10 - 25 days post onset of COVID-19 symptomatic infection. An increased frequency of children presenting with encephalitis and encephalopathy was observed during the Omicron variant predominant period. A poor outcome (no recovery or death) was associated with supplemental oxygen requirement during admission (Odds Ratio: 12.94; p = 0.046). CONCLUSIONS: The spectrum and frequencies of COVID-19 associated neurological disorders in Sri Lanka were similar to that reported from other countries, with strokes and encephalopathy being the commonest. Requiring supplemental oxygen during hospitalisation was associated with a poor outcome.

Subclinical memory impairment in unaffected siblings of patients with dementia.

Objective: Family history of dementia is a known risk factor for dementia. The cognitive performance of unaffected siblings of dementia patients has been poorly studied. We aimed to determine whether clinically unaffected siblings of dementia patients have significant cognitive impairment compared to individuals who do not have first-degree relatives with dementia. Methods: We compared the cognitive performance of 67 patients with dementia (24 males; mean age 69.5), 90 healthy siblings of those patients (34 males; mean age 61.56) and 92 healthy adults (35 males; mean age 60.96) who have no first-degree relatives with dementia. We assessed learning and memory (Rey Auditory Verbal Learning Test (RAVLT)), short-term/working memory (Digit Span) executive functions (Stroop Test) and general intelligence (Raven Progressive Matrices). Test scores were compared among three groups, with regression-based adjustments for age, sex, and education. Results: As expected, the patients with dementia were impaired in all cognitive domains. In the Sibling Group, RAVLT total learning was significantly lower compared to controls (B = -3.192, p = .005). In a subgroup analysis, compared to controls, RAVLT delayed recall was poorer in the siblings of patients with early-onset (<65 years) dementia. No significant differences were observed in other cognitive domains. Conclusion: Clinically unaffected siblings of dementia patients seem to have a selective subclinical impairment in memory encoding. This impairment seems to be more prominent in siblings of patients with early-onset dementia who also have deficits in delayed recall. Future studies are needed to determine if the observed cognitive impairment deteriorates to dementia.

Spontaneously resolving cerebellar syndrome as a sequelae of dengue viral infection: a case series from Sri Lanka.

Sri Lanka is hyperendemic for dengue viral infection. Dengue has a wide spectrum of neurological manifestations including previously reported Sri Lankan cases with a 6th nerve palsy and a cerebellar syndrome from a co-infection with dengue and Epstein-Barr virus. This series describes a spontaneously resolving cerebellar syndrome following a dengue viral infection. Dengue is potentially an important cause of cerebellar syndromes in countries hyperendemic for the disease; patients need further studies to identify the responsible serotypes.

Protective effect of gallic acid on alloxan-induced oxidative stress and osmotic fragility in rats.

In the present study, we investigated the antioxidant effect of gallic acid (GA) on membrane lipid peroxidation and osmotic fragility in alloxan-induced diabetic Wistar rats. GA was administered orally at doses of 5, 10, and 20 mg/kg body weight for 45 days, after which liver and kidney tissues were analyzed for the degree of lipid peroxidation, reduced glutathione, and the activities of antioxidants such as catalase, superoxide dismutase, and glutathione peroxidase. Administration of GA to alloxan-induced diabetic rats reduced the blood glucose level with an increase in the level of insulin. Liver and kidney tissues from diabetic animals exhibited disturbances in antioxidant defense compared with normal rats. GA at a dose of 20 mg/kg b.w. showed a significant effect than that of the other doses. In addition, the results revealed that GA protected the integrity of erythrocyte membrane in diabetic rats as demonstrated by lower percentage of hemolysis and resistance to hydrogen peroxide-induced peroxidation. The anti-hyperglycemic activity of GA in alloxan-induced diabetic rats was also comparable with glibenclamide, a reference drug. These results suggest that GA could provide a beneficial effect on diabetes by decreasing oxidative stress-related diabetic complications.

In vitro cytotoxicity of Gymnema montanum in human leukaemia HL-60 cells; induction of apoptosis by mitochondrial membrane potential collapse.

OBJECTIVES: Gymnema montanum Hook, an Indian Ayurvedic medicinal plant, is used traditionally to treat a variety of ailments. Here, we report anti-cancer effects and molecular mechanisms of ethanolic extract of G. montanum (GLEt) on human leukaemia HL-60 cells, compared to peripheral blood mononuclear cells. MATERIALS AND METHODS: HL-60 cells were treated with different concentrations of GLEt (10-50 µg/ml) and cytotoxicity was assessed by MTT assay. Levels of lipid peroxidation, antioxidants, mitochondrial membrane potential and caspase-3 were measured. Further, apoptosis was studied using annexin-V staining and the cell cycle was analyzed by flow cytometry. RESULTS: GLEt had a potent cytotoxic effect on HL-60 cells (IC50 -20 µg/ml), yet was not toxic to normal peripheral blood mononuclear cells. Exposure of HL-60 cells to GLEt led to elevated levels of malonaldehyde formation, but to reduced glutathione, superoxide dismutase, catalase and glutathione peroxidase activities (P < 0.05). Induction of apoptosis was confirmed by observing annexin-V positive cells, associated with loss of mitochondrial membrane potential. Cell cycle arrest at G0/G1 was observed in GLEt-treated HL-60 cells, indicating its potential at inducing their apoptosis. CONCLUSIONS: Findings of the present study suggest that G. montanum induced apoptosis in the human leukaemic cancer cells, mediated by collapse of mitochondrial membrane potential, generation of reactive oxygen species and depletion of intracellular antioxidant potential.

Antigenotoxic potential of Gymnema montanum leaves on DNA damage in human peripheral blood lymphocytes and HL-60 cell line.

In this study we have evaluated the genoprotective effect of the ethanol extract of Gymnema montanum (GLEt) leaves in human peripheral blood lymphocytes and HL-60 cell line in vitro using the comet assay. DNA damage was induced by treating the cells with H(2)O(2) and methyl methane sulphonate (MMS). GLEt treatment effectively protected the lymphocytes and HL-60 cell line from H(2)O(2)-induced oxidative DNA damage in a dose-dependent manner whereas it was not effective against alkylative DNA damage caused by MMS. The global percent repair efficiency also showed that both pre- and post- GLEt treatment provided effective protection against H(2)O(2) induced DNA damage but not as effective against MMS. At 200 microg ml(-1) level, its repair capacity against H(2)O(2) induced DNA damage was comparable to that of vitamin-C (100 microM). Furthermore, exposure to GLEt reduced the formation of apoptotic cells caused by H(2)O(2), which was demonstrated by the decreased sub-G1-DNA content in cell cycle analysis and apoptotic frequencies of lymphocytes in an annexin-V binding assay. In addition, GLEt was found to have effective peroxide scavenging ability in dose-dependent manner. The protective efficiency of the extract was found to be directly proportional to its total phenolic content. The present study indicates that G. montanum leaves are a significant source of phytochemicals with antigenotoxic and antioxidant activity, and thus has potential therapeutic use.

Antifeedant activity of some pentacyclic triterpene acids and their fatty acid ester analogues.

The 3-O-fatty acid ester derivatives (C(12)-C(18)) of two pentacyclic triterpenic acids, ursolic acid and oleanolic acid, were synthesized under mild esterification conditions in excellent yields (80-85%) and screened for their antifeedant activity, together with the parent acids, against the agricultural pest tobacco caterpillar larvae (Spodoptera litura F) in a no-choice laboratory study. The Urs-12-ene-28-carboxy-3beta-octadecanoate and olean-12-ene-28-carboxy-3beta-hexadecanoate were found to exhibit exceptionally potent antifeedant activities at 50 microg/cm(2) concentration, even after 48 h.