Sandesh Panthi

Sickel cell disease (SCD) is a genetic potentially debilitating disease with global concern. Hydroxyurea is an oral therapeutic agent with proven laboratory and clinical efficacy for sickle cell anemia. It can be speculated that SCD tends to greatly deplete the finances of households in developing countries where there is high level of poverty and inequitable distribution of wealth and resources. To determine direct medical and non-medical cost, we conducted a study to compare standard fixed-dose hydroxyurea with dose escalation to the maximum tolerated dose. A concurrent mixed method design was conducted on patients visiting the Bheri Hospital of Nepalgunj, Nepal who came for checkup of SCD was the study population. The sociodemographic and patient-related questionnaires was utilized for the data collection. Data was analyzed using SPSS version23. Out of 80 patients, the 53.75 patients were male. The median value of Hbs was found to be 69.2. 36 patients were found to be in fixed dose group while other 48 patients fall under the dose escalated group. While observing the lab parameters hemoglobin and fetal hemoglobin is in increasing manner while other blood cell counts were decreased. More number of ADRs are observed in the fixed-dose group with vaso-oclusive pain as a major clinical complication in the people. The overall cost that a patient bear was found to be NRs. 57309.523 ± 16637.095 (i.e. around 600USD) while Nepal’s GDP per capita is around 1400 USD (based on 2023 data). The study suggests hydroxyurea dosing should be maintained properly, and evaluation of laboratory parameters and the clinical complications should be addressed properly. The economic burden seems to be high in the SCD patients. Implementing hydroxyurea, effective administration of other agents and utilizing rigorous treatment approaches have the potential to reduce the overall impact on both patients and healthcare systems.

Pregnancy is the period of time when a fetus develops inside a woman's uterus. When counting from the last menstrual cycle through delivery, a pregnancy typically lasts around 40 weeks, or slightly over 9 months. Pregnancy is divided into three trimesters, as described by healthcare professionals. First trimester: from conception to 12 weeks; second trimester: from 13 to 28 weeks; third trimester: from 29 to 40 weeks. Seizures are a defining feature of the illness, however not all seizures are caused by epilepsy, such as febrile seizures or seizures brought on by drugs. The multilevel categorization of epilepsies was developed to facilitate categorizing epilepsy in varied clinical contexts. There are three types of seizures: those with undetermined onset, generalized onset, and focal onset. The second level is epilepsy type, which introduces the new categories of generalized epilepsy, focal epilepsies, and unknown. A variety of seizure forms, including absence, myoclonic, atonic, tonic, and tonic-clonic seizures, can occur in generalized epilepsies. An epilepsy syndrome diagnosis comes in third place. An epilepsy syndrome is a collection of symptoms that includes seizure types, EEG patterns, and imaging characteristics that frequently co-occur. This review underwent a narrative evaluation, for which papers from the Cochrane library, PubMed, Google Scholar, and Web of Science were gathered. Epilepsy is treated with antiepileptic medications (AEDs). There is evidence that suggests some antiepileptic drugs (AEDs) increase the chance of congenital malformation and induce teratology. The risk of malformation is increased by medications including carbamazepine, phenobarbital, phenytoin, topiramate, and valproate, but not by lamotrigine, gabapentin, levetiracetam, oxcarbazepine, primidone, or zonisamide. Lacosamide, Eslicarbazepine, Clonazepam, Clobazam, and Rivaracetam did not either.

Background and Aim: Patients with Type 2-diabetes condition tend to have multiple medications in various dosage which leads to complex medication regimens. Complexity of regimen results in poor adherence, uncontrolled glycemic value and treatment failure. The research aimed to investigate medication regimen complexity index, medication adherence, and impact of medication regimen complexity on glycemic control and medication adherence.Materials and Methods: A Crossectional Study methods was conducted at Bheri Hospital Nepalgunj, among 145 Diabetes patients. Medication adherence was assessed by using a General Medication Adherence Scale (GMAS Nep-Tool). Medication regimen complexity was assessed by using a Medication Regimen Complexity Index (MRCI) tool. Chi-square test, One-way ANOVA, Paired t-test, and binary logistic regression were used for inferential statistics. Results: This study shows that most of the participants were female and aged group 50-59 years. Hypertension was the most common comorbidity, followed by hypothyroidism. The majority of participants exhibited partial adherence 90 (62.1%) to their medication regimen. It was seen that medications prescribed for diabetes were more complex than non-diabetes medications (Mean±SD MRCI: 8.28±3.155 vs. 4.57±2.107). The negative correlation was seen with diabetes MRCI and medication adherence (r=-0.090). There was statistically significant association between diabetes MRCI and glycemic control, (p. Binary logistic regression revealed that females had lower odds of high MRCI compared to males ( multivariate p-value: 0.014, AOR: 0.403, 95% CI: 0.195-0.832), while sedentary lifestyle showed high Diabetes MRCI (COR: 4.709, 95% CI: 0.962-23.05) and abnormal BMI were associated with higher MRCI (binary p-value: 0.067, COR: 2.30, 95% CI: 0.942-5.65; multivariate p-value: 0.092, AOR: 2.323, 95% CI: 0.878-5.67). Conclusion: Diabetes medications are more complex, reducing adherence and worsening A1C outcomes. Simplifying regimens improves results, with MRCI being valuable for healthcare providers. The medication adherence and therapeutic outcomes can be improved by the improved by the involvement of clinical pharmacist using MRCI.

Aim: Nepal’s medicinal plants are culturally important and have diverse benefits. Senna alata belongs to the family Leguminosae and is a valuable plant utilized for medicinal and ornamental purposes. The aim of the research was to extract Senna alata leaves by successive maceration with various solvents. Methods: In this study, various methods were utilized to evaluate phytochemistry, overall phenolic and flavonoid content, in-vitro antioxidant, anti-inflammatory, cytotoxicity assay, anti-thrombolytic activity, and antibacterial activities. Results: The extractive values of Senna alata were determined as 1.58%, 0.78%, and 5.92% in hexane, ethyl acetate, and methanol, respectively. GC-MS analysis revealed major compounds such as 3-Methylmannoside, Neophytadiene, Campesterol, and Vitamin E in the leaf extract. Qualitative phytochemical screening verified the tannin content, carbohydrates, flavonoids, cardiac glycosides, glycosides, and saponins in the methanol extract. The total phenolic and flavonoid values were 46.36±4.5 mg GAE/gm and 480.4±3.055 QE/gm of dried extract, respectively. The extract exhibited significant antioxidant and anti-inflammatory activities, with IC50 values of 29.81 and 9.93, respectively. Furthermore, it demonstrated cytotoxic activity with an LC50 value of 767.85 in the brine shrimp bioassay. In terms of thrombolytic activity, the extract showed clot lysis percentages of 7.89% and 10.13% at concentrations of 10 mg/ml and 25 mg/ml, respectively. Conclusion: In conclusion, the methanolic extract of Senna alata leaves displayed therapeutic potential, including antioxidant, anti-inflammatory, cytotoxic, thrombolytic, and antibacterial effects. The existence of several chemicals via GC-MS analysis also verified plant's potential for therapeutic use.

Background of the study: Depression is a prevalent mental disorder characterized by various symptoms, including low mood, lack of pleasure, changes in appetite and sleep, and difficulty concentrating. Antidepressants are commonly used to manage depression as well as other related disorders, such as anxiety and somatoform disorders. This study aimed to investigate the adverse drug effects experienced by adult patients who were using antidepressants at Chitwan Medical College Teaching Hospital in Nepal. Methods: This study was a retro-prospective, observational study consisting of 117 adult patients under antidepressant medication. The adverse drug profile for the patients was collected using an antidepressant side effect checklist developed by the NHS foundation trust. Statistical analysis was performed using SPSS version 20. Result: The study group consisted of adult patients using antidepressants at Chitwan Medical College Teaching Hospital, Chitwan, Nepal. The mean age of the group was 40.9 ± 12.8, with 63.2% females and 36.7% males. The most common conditions for which antidepressants were prescribed were depression (49.5%), anxiety disorder (31.6%), and somatoform disorder (13.6%). Amitriptyline was the most commonly used medication in monotherapy (64.1%), followed by escitalopram and sertraline. Dry mouth, weight gain, drowsiness, blurred vision, problems with sexual function, and an increase in appetite were the most commonly reported adverse effects. The incidence of certain adverse effects was higher in the multiple therapy group than in the monotherapy group (p < 0.05). Conclusion: The incidence of adverse drug effects is high in patients taking antidepressants, especially those receiving multiple medications. Educating patients about common side effects and prescribing monotherapy whenever possible are crucial in reducing the incidence.

The Special Issue “Animal Models of Neurological Disorders: Where Are We Now

Absence seizures are associated with generalised synchronous 2.5–4 Hz spike-wave discharges causing brief and sudden alteration of awareness during childhood, which is known as childhood absence epilepsy (CAE). CAE is also associated with impaired learning, psychosocial challenges, and physical danger. Absence seizures arise from disturbances within the cortico-thalamocortical (CTC) network, including dysfunctional feed-forward inhibition (FFI); however, the precise mechanisms remain unclear. In epileptic stargazers, a genetic mouse model of CAE with chronic seizures, levels of γ-aminobutyric acid (GABA), and expression of GABA receptors are altered within the CTC network, implicating altered GABAergic transmission in absence seizures. However, the expression of GABA synthesising enzymes (GAD65 and GAD67) and GABA transporters (GAT-1 and 3) have not yet been characterised within absence seizure models. We found a specific upregulation of GAD65 in the somatosensory cortex but not the thalamus of epileptic stargazer mice. No differences were detected in GAD67 and GAT-3 levels in the thalamus or somatosensory cortex. Then, we assessed if GAD65 upregulation also occurred in Gi-DREADD mice exhibiting acute absence seizures, but we found no change in the expression profiles of GAD65/67 or GAT-3. Thus, the upregulation of GAD65 in stargazers may be a compensatory mechanism in response to long-term dysfunctional FFI and chronic absence seizures.

After publication of the original article [1], it came to our attention that Professor Junyang Jung was omitted from the authorship.

Hydrogen Sulfide (H2S) and Nitric Oxide (NO) have become recognized as important gaseous signaling molecules with enormous pharmacological effects, therapeutic value, and central physiological roles. NO is one of the most important regulators of the pathophysiological condition in central nervous system (CNS). It is critical in the various functioning of the brain; however, beyond certain concentration/level, it is toxic. H2S was regarded as toxic gas with the smell like rotten egg. But, it is now regarded as emerging neuroprotectant and neuromodulator. Recently, the use of donors and inhibitors of these signaling molecules have helped us to identify their accurate and precise biological effects. The most abundant neurotransmitter of CNS (glutamate) is the initiator of the reaction that forms NO, and H2S is highly expressed in brain. These molecules are shedding light on the pathogenesis of various neurological disorders. This review is mainly focused on the importance of H2S and NO for normal functioning of CNS.

Short-lived reactive nitrogen species and reactive oxygen species have acquired significant attention in the field of biomedical science. Nitric oxide (NO), which was thought to be an unstable gas and pollutant, is now regarded as a gas transmitter like H2S and CO. NO is synthesized inside the mammalian body by l-arginine via three different isoforms of NO synthase whereas pyruvate is a glycolysis product and substrate for TCA cycle. Due to poor solubility and stability, therapeutic potential of pyruvate is limited. Ethyl pyruvate (EP) is now considered as a suitable replacement of pyruvate. In this paper, we will try to focus the effect of NO and EP in Schwann cell dedifferentiation, proliferation, nerve degeneration, and regeneration during Wallerian degeneration (WD) of peripheral nerve injury along with their neuroprotective effects, cardiovascular functioning, support in hepatic complication, etc.