Evaluation of anxiolytic effect of furosemide in Albino rats

Background: Anxiety disorders are the most prevalent class of psychiatric condition. Medications commonly given for treatment can elicit several central nervous system (CNS) side-effects that patients find difficult to tolerate. So there is a need for new pharmacotherapeutic approaches to treat anxiety with greater efficacy and fewer side effects. Hence this study has been taken up to evaluate the anxiolytic effect of furosemide at three different doses (75mg/kg, 150mg/kg and 200mg/kg) in Albino rats.Methods: After obtaining approval from the institutional animal ethical committee 30 Albino rats weighing about 150-200gm were taken and divided into 5 groups of 6 rats each. Group 1: Normal Saline 10ml/kg (control); Group 2: Diazepam 2mg/kg (standard); Group 3: Furosemide 150mg/kg (test group 1); Group 4: Furosemide 200mg/kg (test group 2); Group 5: Furosemide 75mg/kg + Diazepam 1mg/kg (sub threshold dose). The anxiolytic activity of furosemide was tested by elevated plus maze and digital actophotometer models. Data was analysed using one way ANOVA followed by Posthoc Tukey’s test.Results: Furosemide (150mg/kg and 200mg/kg) have shown significant increase in open arm entries (p<0.05) and time spent in open arm (p<0.05) compared to control. Also furosemide (150mg/kg and 200mg/kg) have shown statistically significant decrease in locomotor activity (p<0.05) compared to control in actophotometer model. Potentiation of time spent and number of entries in open arm and decrease in locomotor activity were noticed when sub threshold doses of combination of diazepam and furosemide were used.Conclusions: These results suggest that furosemide possesses significant anxiolytic activity at both the doses. Furosemide given in sub threshold dose potentiates the antianxiety effect of sub threshold dose of diazepam when used in combination. Hence, after further studies, furosemide can be used as an anxiolytic drug

Evaluation of efficacy of Carica papaya leaf extracts to increase platelet count in hydroxyurea induced thrombocytopenia in Albino rats

Background: Dengue is an infectious disease associated with high mortality and morbidity. Being a viral disease, there is no specific drug available for treatment. There are some reports that Carica papaya leaf extract may improve the clinical condition of dengue patients. However, to support this, at present, there is no systematically searched and synthesized evidence available. Hence this study was undertaken to compare the efficacy of commercial preparation of Carica papaya leaves with freshly prepared Carica papaya leaf extracted.Methods: 48 albino rats were randomly divided into eight groups of six each. Thrombocytopenia was induced by giving hydroxyurea (15mg/kg) orally. Group I and II served as saline and toxic control group respectively. Other six groups were given two different doses of either commercial extract or fresh extract orally for five days. 1ml of blood was withdrawn at baseline,3rd and 6th day of the study. Platelet, WBC, RBC count, clotting and bleeding time were determined.Results: Mean platelet count increased significantly on day 6 in both low dose (2.06 to 4.93lakh/mm3) and human equivalent dose (2.73 to 7.66lakh/mm3) of commercial extract groups compared to the toxic control group (p<0.05). Similarly, the mean platelet count increased significantly for human equivalent dose in fresh leaf extract group (3.17 to 4.69lakh/mm3) but the increase in low dose fresh extract (3.28 to 3.76lakh/mm3) was not significant. There was no significant rise in mean platelets count, mean RBC count, WBC count, decrease in mean bleeding and clotting time between commercial extract and fresh leaf extract group for both low dose and human equivalent dose.Conclusions: Efficacy of fresh leaf extract of Carica papaya was not inferior to commercial available preparation. Fresh Carica papaya leaf extract no doubt offers a potential therapeutic efficacy which is cost effective, more affordable and accessible treatment in patients with thrombocytopenia

RRM adjacent TARDBP mutations disrupt RNA binding and enhance TDP-43 proteinopathy

Amyotrophic lateral sclerosis (ALS) presents with focal muscle weakness due to motor neuron degeneration that becomes generalized,leading to death from respiratory failure within 3–5 years from symptom onset. Despite the heterogeneity of aetiology, TDP- 43 proteinopathy is a common pathological feature that is observed in 495% of ALS and tau-negative frontotemporal dementia(FTD) cases. TDP-43 is a DNA/RNA-binding protein that in ALS and FTD translocates from being predominantly nuclear to formdetergent-resistant, hyperphosphorylated aggregates in the cytoplasm of affected neurons and glia. Mutations in TARDBP accountfor 1–4% of all ALS cases and almost all arise in the low complexity C-terminal domain that does not affect RNA binding andprocessing. Here we report an ALS/FTD kindred with a novel K181E TDP-43 mutation that is located in close proximity to the RRM1 domain. To offer predictive gene testing to at-risk family members, we undertook a series of functional studies to characterizethe properties of the mutation. Spectroscopy studies of the K181E protein revealed no evidence of significant misfolding.Although it is unable to bind to or splice RNA, it forms abundant aggregates in transfected cells. We extended our study to includeother ALS-linked mutations adjacent to the RRM domains that also disrupt RNA binding and greatly enhance TDP-43 aggregation,forming detergent-resistant and hyperphosphorylated inclusions. Lastly, we demonstrate that K181E binds to, and sequesters, wild-type TDP-43 within nuclear and cytoplasmic inclusions. Thus, we demonstrate that TDP-43 mutations that disrupt RNAbinding greatly enhance aggregation and are likely to be pathogenic as they promote wild-type TDP-43 to mislocalize andaggregate acting in a dominant-negative manner. This study highlights the importance of RNA binding to maintain TDP-43solubility and the role of TDP-43 aggregation in disease pathogenesis

Evaluation of anxiolytic effect of furosemide in Albino rats

Background: Anxiety disorders are the most prevalent class of psychiatric condition. Medications commonly given for treatment can elicit several central nervous system (CNS) side-effects that patients find difficult to tolerate. So there is a need for new pharmacotherapeutic approaches to treat anxiety with greater efficacy and fewer side effects. Hence this study has been taken up to evaluate the anxiolytic effect of furosemide at three different doses (75mg/kg, 150mg/kg and 200mg/kg) in Albino rats.Methods: After obtaining approval from the institutional animal ethical committee 30 Albino rats weighing about 150-200gm were taken and divided into 5 groups of 6 rats each. Group 1: Normal Saline 10ml/kg (control); Group 2: Diazepam 2mg/kg (standard); Group 3: Furosemide 150mg/kg (test group 1); Group 4: Furosemide 200mg/kg (test group 2); Group 5: Furosemide 75mg/kg + Diazepam 1mg/kg (sub threshold dose). The anxiolytic activity of furosemide was tested by elevated plus maze and digital actophotometer models. Data was analysed using one way ANOVA followed by Posthoc Tukey’s test.Results: Furosemide (150mg/kg and 200mg/kg) have shown significant increase in open arm entries (p&lt;0.05) and time spent in open arm (p&lt;0.05) compared to control. Also furosemide (150mg/kg and 200mg/kg) have shown statistically significant decrease in locomotor activity (p&lt;0.05) compared to control in actophotometer model. Potentiation of time spent and number of entries in open arm and decrease in locomotor activity were noticed when sub threshold doses of combination of diazepam and furosemide were used.Conclusions: These results suggest that furosemide possesses significant anxiolytic activity at both the doses. Furosemide given in sub threshold dose potentiates the antianxiety effect of sub threshold dose of diazepam when used in combination. Hence, after further studies, furosemide can be used as an anxiolytic drug

FLAXSEED OIL ALONE AND AS AN ADJUVANT WITH PHENYTOIN IN MES-INDUCED SEIZURES IN ALBINO RATS

 Objective: The objective of this study to evaluate the anticonvulsant activity of flaxseed oil alone and as an adjuvant to phenytoin sodium.Methods: A total of 24 albino rats were used for this study. Four groups - control, standard (phenytoin sodium), test (flaxseed oil), and flaxseed oil along with phenytoin were made with six rats in each group. Maximal electroshock seizures 60-Hz AC of 150 mA intensity for 0.2 s were induced using an electroconvulsiometer with ear electrodes 60 min after oral drug administration. Duration of tonic hind limb extension (THLE) in seconds was used as a measure of seizures induced.Results: The mean duration of THLE in 4 groups was 11.66 (Group I), 5.67 (Group II), 3.85 (Group III), and 2.69 (Group IV). Duration of THLE was reduced in flaxseed oil group (P &lt; 0.000) compared to both control and standard. Other parameters such as regain of righting reflex and recovery time also showed improvement. The group where flaxseed oil was used as an adjuvant to phenytoin also showed significant anticonvulsant activity. It showed a greater reduction in the parameters compared to either drug alone.Conclusion: The study showed that flaxseed oil possesses marked anticonvulsant activity when used alone and as an adjuvant to phenytoin. This study shows the potential of flaxseed oil in generalized tonic-clonic seizure

Evaluation of efficacy of Carica papaya leaf extracts to increase platelet count in hydroxyurea induced thrombocytopenia in Albino rats

Background: Dengue is an infectious disease associated with high mortality and morbidity. Being a viral disease, there is no specific drug available for treatment. There are some reports that Carica papaya leaf extract may improve the clinical condition of dengue patients. However, to support this, at present, there is no systematically searched and synthesized evidence available. Hence this study was undertaken to compare the efficacy of commercial preparation of Carica papaya leaves with freshly prepared Carica papaya leaf extracted.Methods: 48 albino rats were randomly divided into eight groups of six each. Thrombocytopenia was induced by giving hydroxyurea (15mg/kg) orally. Group I and II served as saline and toxic control group respectively. Other six groups were given two different doses of either commercial extract or fresh extract orally for five days. 1ml of blood was withdrawn at baseline,3rd and 6th day of the study. Platelet, WBC, RBC count, clotting and bleeding time were determined.Results: Mean platelet count increased significantly on day 6 in both low dose (2.06 to 4.93lakh/mm3) and human equivalent dose (2.73 to 7.66lakh/mm3) of commercial extract groups compared to the toxic control group (p&lt;0.05). Similarly, the mean platelet count increased significantly for human equivalent dose in fresh leaf extract group (3.17 to 4.69lakh/mm3) but the increase in low dose fresh extract (3.28 to 3.76lakh/mm3) was not significant. There was no significant rise in mean platelets count, mean RBC count, WBC count, decrease in mean bleeding and clotting time between commercial extract and fresh leaf extract group for both low dose and human equivalent dose.Conclusions: Efficacy of fresh leaf extract of Carica papaya was not inferior to commercial available preparation. Fresh Carica papaya leaf extract no doubt offers a potential therapeutic efficacy which is cost effective, more affordable and accessible treatment in patients with thrombocytopenia

Risk of Aneurysm Rupture (ROAR) study: protocol for a long-term, longitudinal, UK multicentre study of unruptured intracranial aneurysms

Introduction Unruptured intracranial aneurysms (UIA) are common in the adult population, but only a relatively small proportion will rupture. It is therefore essential to have accurate estimates of rupture risk to target treatment towards those who stand to benefit and avoid exposing patients to the risks of unnecessary treatment. The best available UIA natural history data are the PHASES study. However, this has never been validated and given the known heterogeneity in the populations, methods and biases of the constituent studies, there is a need to do so. There are also many potential predictors not considered in PHASES that require evaluation, and the estimated rupture risk is largely based on short-term follow-up (mostly 1 year). The aims of this study are to: (1) test the accuracy of PHASES in a UK population, (2) evaluate additional predictors of rupture and (3) assess long-term UIA rupture rates.Methods and analysis The Risk of Aneurysm Rupture study is a longitudinal multicentre study that will identify patients with known UIA seen in neurosurgery units. Patients will have baseline demographics and aneurysm characteristics collected by their neurosurgery unit and then a single aggregated national cohort will be linked to databases of hospital admissions and deaths to identify all patients who may have subsequently suffered a subarachnoid haemorrhage. All matched admissions and deaths will be checked against medical records to confirm the diagnosis of aneurysmal subarachnoid haemorrhage. The target sample size is 20 000 patients. The primary outcome will be aneurysm rupture resulting in hospital admission or death. Cox regression models will be built to test each of the study’s aims.Ethics and dissemination Ethical approval has been given by South Central Hampshire A Research Ethics Committee (21SC0064) and Confidentiality Advisory Group support (21CAG0033) provided under Section 251 of the NHS Act 2006. The results will be disseminated in peer-reviewed journals.Trial registration number ISRCTN17658526