Luracidone hydrochloride exhibits pH-sensitive solubility, which limits its absorption and results in poor oral bioavailability. To address this problem, the present study focused on the formulation of gastro retentive floating pellets of luracidone hydrochloride using the extrusion-speronization technique to enhance gastric retention, solubility, and plasma concentration. The 33 Box-Behnken design was applied to optimize the formulation batch. For that, the levels of HPMC K100 (X1), ethyl cellulose (X2), and spheronization speed (X3) were varied, and their influence was evaluated on aspect ratio (Y1), floating time (Y2), and in vitro % drug release (Y3). The observed optimized batch was subsequently coated with a 5 % ethyl cellulose and subjected to a comprehensive physicochemical evaluation with % drug release and in vivo pharmacokinetic assessment. The drug release data observed that the coated luracidone hydrochloride pellets release the drug over 18 h, whereas the uncoated pellets release up to 12 h. The ethyl cellulose coating also improved the buoyancy, which minimizes dose dumping and improves the absorption window of luracidone hydrochloride in the upper GI tract. The relative oral bioavailability of uncoated and coated pellets was significantly higher, up to 5-fold and 7-fold, respectively, compared to pure luracidone hydrochloride. It strongly supports the hypothesis that coated luracidone hydrochloride gastro retentive floating pellets could enhance oral bioavailability instead of pure lurasidone hydrochloride. Keywords Lurasidone hydrochloride, spheronization, gastro retentive pellets, buoyancy, oral bioavailability
Flavanones represent an important class of naturally inspired scaffolds with diverse pharmacological activities, including notable anticancer potential. Structural modification of the flavanone core offers opportunities to enhance biological performance and identify new lead molecules. In the present study, a series of nine flavanone-arylhydrazone derivatives was synthesised through the condensation of substituted flavanones with corresponding phenylhydrazines under reflux conditions. The synthesised compounds were obtained in good yields and were structurally confirmed using infrared spectroscopy, nuclear magnetic resonance spectroscopy, and mass spectrometry, which collectively verified the integrity of the hydrazone linkage and aromatic substitutions. The derivatives were evaluated for in vitro cytotoxicity against two human breast cancer cell lines, michigan cancer foundation-7 (hormone-dependent) and MDA-MB-231 (triple-negative), using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Tamoxifen served as the reference standard. All compounds exhibited dose-dependent cytotoxicity, with variable responses across both cell lines. Among them, compounds 3 and 1 demonstrated the highest activity, with IC50 values of 33.54±2.2 µM and 36.60±2.4 µM in Michigan cancer foundation-7 cells and 41.08±2.6 µM and 44.21±2.7 µM in MDA-MB-231 cells, respectively. Structure-activity analysis indicated that derivatives bearing electron-withdrawing substituents, such as nitro and halogens, displayed comparatively enhanced potency. The findings emphasise the possible use of flavanone–arylyhydrazone hybrids as promising anticancer candidates. Compounds 3 and 1, in particular, may serve as lead molecules for further mechanistic investigations and optimisation studies aimed at developing new therapeutic agents for breast cancer. Keywords Flavanone, hydrazone, breast neoplasms, Michigan cancer foundation-7 Cells, MDAMB-231 cells
Cerebral toxoplasmosis is a significant cause of morbidity and mortality, especially in immunocompromised individuals, with treatment hindered by poor drug bioavailability in the brain, systemic side effects, and relapse risk. This study aimed to develop an effective nose-to-brain therapeutic strategy using poly (ε-caprolactone) nanoparticles loaded with trimethoprim and sulfamethoxazole and coated with chitosan. Trimethoprim and sulfamethoxazole and coated with chitosan were synthesized, optimized, and coated with 0.5 % CS. Trimethoprim and sulfamethoxazole and coated with chitosan were characterized using analytical techniques, and their in vitro drug release and efficacy against Toxoplasma gondii-infected rat primary astrocytes were evaluated. For in vivo studies, trimethoprim and sulfamethoxazole and coated with chitosan were labeled with IR820, administered intranasally to mice, and their biodistribution was monitored in live animals to assess nose-to-brain delivery. TMP-SMX-NPsCS showed 174 nm, a 0.14 polydispersity index, and +31 mV zeta potential. Encapsulation efficiencies were 88.93 % for TMP and 85.23 % for SMX. FTIR and thermal analysis confirmed uniform drug dispersion and successful CS coating. In vitro drug release studies showed sustained release of both drugs over 24 hours under simulated nasal conditions. trimethoprim and sulfamethoxazole and coated with chitosan treatment maintained 72% cell viability compared to untreated controls. In vivo imaging and ex vivo analysis in mice confirmed brain accumulation and limited systemic distribution of IR820-labeled trimethoprim and sulfamethoxazole and coated with chitosan after intranasal administration. These findings suggest that intranasal delivery of trimethoprim and sulfamethoxazole and coated with chitosan is a promising strategy for expanding the therapeutic arsenal against cerebral toxoplasmosis by enabling direct drug delivery to the brain. Keywords Cerebral toxoplasmosis, trimethoprim, sulfamethoxazole, chitosan, nanoparticles coated with chitosan, intranasal administration, nose-to-brain delivery
Skin cancer is one of the leading and most significant threats to the current scenario, mainly due to global warming occurring across the world. Anticancer drugs either completely kill most cancer cells or, in some ways, modify their growth. However, the selectivity of most medications is constrained, which makes them the most toxic drugs used in therapy. However, technologies and innovations have attracted the attention of contemporary developments with the help of numerous discoveries in nearly every subject. Additionally, vesicular carriers have been explored for drug discovery in a protracted manner. These carriers improve the drug's permeability, ensure that the drug is delivered at the target site and from approaches such as gels and patches, and, for this reason, nullify the troubles related to the distribution, resistance, specificity, selectivity, and systemic toxicity of drugs. This review highlights the etiology, therapies, and briefings of various vesicular carriers for the treatment of skin cancer. Keywords Transdermal drug delivery, carriers, vesicular, skin, cancer
BACKGROUND:The study aimed to analyze the current trends and spatiotemporal dynamics of research on carrageenan and digestive problems through a bibliometric study from 2019 to 2024.MATERIALS AND METHODS:The literature published on carrageenan and digestive issues from the period of January 2019 until July 2024 was examined using an observational and descriptive approach. The use of a quantitative approach was made in relation to authorship distribution and collaboration, country collaboration, and the evolution of themes. A search of the Scopus database was conducted with different keywords of "Carrageenan" and "Digestive problems." Analysis and visualization of the data were done with the use of SciVal and RStudio software.RESULTS:Between 2019 and 2024, a significant increase in publication activity occurred, with associated variations in publication types and pronounced growth in international collaboration. In regard to scientific production, there was an average year-on-year increase of 18.98%, with an average age of the papers of 3.2 years and an average of 15.72 citations per article. A total of 889 authors produced the articles, with an average of 6.71 co-authors per paper and 21.33% international collaborations. Notable institutions producing articles include the Ocean University of China, which produced seven articles, and Jimei University, which produced five articles. The scientific production was highest in China (40), followed by Brazil and Japan, and while most authors contributed a single article, there was a lack of equal scientific productivity accumulated in the articles.CONCLUSIONS:The results highlight both the importance and the need to investigate carrageenan and its impact on digestive issues that might yield exciting avenues of research. The number of publications being produced regarding this foundational aspect of research continues to be relevant. The examination of literature also illustrated the key role of international collaborations and changing research agendas in dealing with the challenges related to digestive problems.
Abstract: Nivolumab, a human IgG4 PD-1 immune checkpoint inhibitor antibody, blocks PD-1 and can restore anticancer immune responses by impairing T-cell suppression via the PD-1 pathway. Nivolumab is generally well-tolerated, with fewer treatment-related adverse events (AEs) than other systemic therapies. Here we report a case of nivolumab-induced folliculitis involving the lower limbs in a 35-year-old male. The patient had multiple follicular-based pustules over the bilateral legs with surrounding erythema. The patient was treated with topical steroids, which resulted in complete resolution.
OBJECTIVES:The objective of the study was to assess the burden of polypharmacy and potentially inappropriate medications (PIMs) among geriatric patients and evaluate the impact of a structured deprescribing approach in these patients. SUBJECTS AND METHODS:Elderly outpatients (≥60 years) with polypharmacy were included. Data on prescribed, over-the-counter (OTC), and traditional medicines were collected through a structured questionnaire and detailed patient interviews. Deprescribing was carried out using Sivagnanam G's "S and S" approach (Seek, Screen, Save, Sever, Sensitize, and Supervise) adapted from Scott et al. RESULTS:Among 385 participants, polypharmacy was prevalent in 182 participants (47.27%) with a mean of 6.5 drugs/prescription. Among participants with polypharmacy, PIMs were noted in 131 (72%) with an average of 1.64 PIMs identified per each inappropriate prescription. PIMs increased with an increase in the number of comorbidities and medication count. A total of 215 PIMs were identified and recommended for deprescribing. These were mainly drugs to be avoided in the elderly (34.88%), OTC PIMs (17.21%), traditional medicines (13.02%), and drug-drug interactions (9.77%). Deprescribing reduced the mean drug count per prescription to 4.86 with a potential to decrease adverse drug reactions by 16.4%, and also lowered daily prescription costs from INR 51.91 to INR 32.70, saving INR 576.42 per patient per month. CONCLUSION:Polypharmacy and PIMs are widely prevalent among elderly patients, significantly increasing the risk of ADEs. Structured deprescribing effectively reduced medication burden, improved safety, and decreased healthcare costs. These findings highlight the need for routine deprescribing interventions to optimize geriatric medication management.
AIMS:Despite decades of proven safety of paracetamol, serious and rare reactions such as Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) often occur in the Indian population. The current study aimed to understand the safety profile of this relatively safer drug, paracetamol, with respect to rare and serious adverse events, SJS/TEN, based on data collected from the Indian population through the Pharmacovigilance Programme of India.METHODS:The collected, collated and analyzed all Individual Case Safety Reports with the use of paracetamol from the Indian population for the period January 1, 2010, to December 31, 2021, were reported to VigiBase and analyzed using the WHO database, VigiLyze.RESULTS:Analysis of the reported data showed that 313 SJS/TEN adverse events were associated with the use of paracetamol. Disproportionality analysis of paracetamol-induced SJS/TEN reactions in the Indian population using the Proportional Reporting Ratio (PRR), reporting odds ratio, and the information component indicated higher risk of paracetamol in the Indian population.CONCLUSIONS:The findings provide crucial insights into the extent of rare and infrequent SJS/TEN associated with the use of paracetamol in the Indian population. Owing to the seriousness of reaction and the widespread use of paracetamol for fever-like illness, the prescribing physicians, pharmacists, and other healthcare professionals should closely monitor patients administered paracetamol for this potential rare reaction, SJS/TEN.
OBJECTIVE:Our research aims to evaluate the important role of glutamine (Gln) in alcohol (ethanol)-induced liver damage. MATERIALS AND METHODS:In our study, the mice were simultaneously divided into normal group, alcohol group, and Gln+alcohol group. After different treatments, we detected alanine aminotransferase (ALT), aspartate aminotransferase (AST), and liver index. Then, some histopathological examination was used to observe the damage of liver tissue, glycogen, and liver cell apoptosis in mice. In addition, the expression of apoptosis-related proteins Bcl-2, Bax, Caspase3, heat stress protein 70 (HSP70), cytochrome cytochrome P450-2E1, NFκB pathway-related proteins IkB-a, NFκB-p65, and tumor necrosis factor-α were detected in different groups by western blotting. The experiment in vitro, we used normal hepatocytes L02, after treatment with alcohol and Gln for 24 h, carried out CCK-8 cell proliferation detection and western blotting to detect the expression of related proteins. RESULTS:Our results showed that, in serological testing, Gln can significantly reduce the levels of ALT, AST, and liver index in Gln+alcohol group; and in the histopathological examination, Gln can increase the glycogen content and decrease the apoptosis rate in Gln+alcohol group. In addition, the differential expression of IκBα, NFκB-p65, and other factors in Western blotting shows that the NFκB signaling pathway plays important role in acute alcoholic liver injury. CONCLUSIONS:Our results showed that Gln played an important protective role in alcohol-induced liver injury in mice by regulating glycogen stores, apoptosis, anti-oxidative stress and inhibiting NF-κB signaling pathways in liver cells.
PURPOSE:This study aimed to evaluate whether the addition of ketamine to an etomidate infusion could attenuate the reduction in serum cortisol levels compared to etomidate alone in patients undergoing elective surgical procedures. SUBJECTS AND METHODS:Eighty patients aged 18-60 years undergoing elective surgery were randomized into two groups. Group E (n = 40) received etomidate infusion 50 mcg/kg/min till the patient was induced. Group KE (n = 40) received a combined infusion of etomidate (1 mg/dL) + ketamine (5 mg/mL) at a rate of 50 mcg/kg/min of etomidate. The primary aim was to estimate serum cortisol levels at baseline, 4 h, 12 h, and 24 h postinduction. RESULTS:The mean post-induction cortisol levels were significantly lower (p-value < 0.001) in Group E (8 ± 2.54 mcg/dL at 4 hours, 7.06 ± 2.57 mcg/dL at 12 hours, and 8.23 ± 3.1 mcg/dL at 24 hours) compared to Group KE (10.14 ± 1.96 mcg/dL at 4 hours, 10.07 ± 2.48 mcg/dL at 12 hours, and 11.27 ± 2.14 mcg/dL at 24 hours) with a comparable baseline cortisol concentrations (12.95 ± 2.64 mcg/dL) in Group E and (11.74 ± 2.11 mcg/dL) in Group KE. The serum cortisol levels decreased by approximately 39% in Group E and by around 17% in Group KE at 4 h postinduction. CONCLUSION:The addition of ketamine to an etomidate induction regimen decreases etomidate-induced adrenal suppression while preserving anesthetic efficacy and maintaining hemodynamic stability.
Abstract: Tapentadol, a dual-action opioid, is increasingly used for pain management in acute pancreatitis (AP). Although its common side effects are well-documented, cutaneous reactions are rare. We report a 30-year-old gentleman with AP who developed generalized urticaria following oral tapentadol use. The patient had no prior history of atopy or drug allergies. The rash resolved after discontinuation of tapentadol and administration of a short course of corticosteroids and antihistamines. Cutaneous reactions to tapentadol are extremely rare but should be recognized promptly to ensure timely management and prevent unnecessary investigations.
Abstract: Chronic pain management continues to challenge clinicians due to limitations in efficacy and tolerability of current pharmacological therapies. Suzetrigine, a first-in-class selective sodium channel blocker, has emerged as a promising agent for the treatment of neuropathic and chronic pain syndromes. Preclinical and clinical data highlight suzetrigine’s unique sodium channel selectivity, reduced central nervous system side effects, and encouraging efficacy signals in neuropathic pain, trigeminal neuralgia, and refractory pain states. Early-phase trials report favorable safety and tolerability compared to conventional sodium channel blockers. Suzetrigine represents a promising new analgesic agent with a novel mechanism of action. Further Phase 3 studies are warranted to establish its role in pain medicine.
ABSTRACT:Warfarin is a widely used oral anticoagulant with a narrow therapeutic index and multiple drug-drug interactions that may significantly alter its anticoagulant effect. Torsemide, a loop diuretic commonly prescribed for heart failure and fluid overload, shares metabolic pathways with warfarin, raising the possibility of clinically significant interactions. However, the evidence regarding this interaction remains limited and inconsistent. A 66-year-old male with a history of type 2 diabetes mellitus, hypertension, chronic kidney disease, and prior aortic valve replacement on chronic warfarin therapy presented with extensive soft tissue necrosis of the left leg following minor trauma. During hospitalization, warfarin (3 mg once daily) and Torsemide (20 mg once daily) were initiated concurrently. Subsequently, the patient developed a progressive elevation in international normalized ratio (INR), necessitating repeated fresh frozen plasma transfusions due to increased bleeding risk. Despite supportive management, INR remained elevated. Torsemide was discontinued and replaced with furosemide, after which a gradual stabilization of INR levels was observed. The patient later required left above-knee amputation due to worsening necrosis but recovered following multidisciplinary management. Assessment using the Naranjo Adverse Drug Reaction Probability Scale suggested a possible interaction between warfarin and Torsemide. This case highlights a potential interaction between warfarin and Torsemide resulting in elevated INR and increased bleeding risk. Clinicians should exercise caution and ensure close INR monitoring when initiating Torsemide in patients receiving warfarin therapy.
BACKGROUND:Recent research indicates that non-steroidal anti-inflammatory drugs may interfere in coagulation process and platelet aggregation. However, the potential of piroxicam in thrombotic and cardiopulmonary disorders remained unexplored. OBJECTIVES:To bridge this knowledge gap, the current study was conducted to assess the potential of piroxicam as antithrombotic and cardiopulmonary protective agent using multi-level approaches. MATERIALS AND METHODS:Piroxicam was docked against 16 key proteins involved in thrombotic and cardiopulmonary conditions. Its antiplatelet effect was evaluated by arachidonic acid (AA) and adenosine diphosphate (ADP)-induced aggregation while its effect on coagulation parameters were also evaluated. Cardiopulmonary protective effect in rats was investigated through isoproterenol induced myocardial infarction (MI) and self-embolus induced pulmonary embolism (PE). RESULTS:Strong binding interactions were identified, with docking energies of ≥-9.0 kcal/mol noted for cyclooxygenase (COX) 1, glycopotein-IIb/IIIa, antithrombin-III, COX-2, and nuclear factor Kappa-B (NFkB). Piroxicam significantly inhibited AA and ADP-induced platelet aggregation (IC50: 0.68 and 24.9 μM) and also prolonged the prothrombin, activated partial thromboplastin, thrombin, and clot lysis time. Piroxicam markedly and in a dose-related manner lowered MI and PE associated serum markers in experimental rats. Piroxicam further safeguarded cardiac and pulmonary tissues from infarction and histopathological injury through the suppression of oxidative imbalance and inflammatory activity. This protective outcome was also due to reduced expression of tissue necrosis factor-α, NFkB, COX-2, NLRP3, and platelet-derived growth factor-β, verified using immunohistochemistry, enzyme-linked immunosorbent assay, and real-time polymerase chain reaction RT-PCR techniques. CONCLUSIONS:These results indicate the prophylactic potential of piroxicam in cardiopulmonary thrombotic disorders.
INTRODUCTION:Valproic acid (VPA) is a widely prescribed first-generation antiepileptic drug. It can induce different liver adverse effects (AEs) which range from mild to severe. MATERIALS AND METHODS:A retrospective study was conducted by collecting 9-year reports (from January 2015 to June 2023) of VPA-associated hepatic AEs. It was collected in the Regional Center of Pharmacovigilance of Sfax (Tunisia). Causality was evaluated with the French Bégaud et al. imputability method. Plasma VPA concentrations were measured using an automated enzyme immunoassay (INDIKO). RESULTS:We collected the eight cases of hepatic cytolysis with varying severity: Six had mild elevations of liver enzymes, one presented with moderately severe cytolysis and one case was fatal. There management strategies were guided by both transaminase levels and VPA concentrations. For those with alanine aminotransferase levels ≥5 times the upper limit of normal (ULN), we conducted the drug discontinuation. However, for patients with lower levels of transaminases, plasma VPA level measurement was recommended. The concentrations were within or near the ULN. Management consisted of either withdrawal or dose reduction, depending on associated clinical symptoms. Additional investigations to rule out nondrug-related causes performed in five cases were negatives. Most patients recovered favorable outcome after discontinuation or VPA dose reduction. CONCLUSION:Management of VPA-induced hepatic cytolysis requires integrating the severity of liver enzyme elevations, plasma drug level measurements, and the results of etiological investigation to guide the clinical decisions.
OBJECTIVES:This study was set out to screen the cytotoxic activity of three extracts of two plants against three cancer cell lines. METHODS:Cytotoxic activity of three extracts of these two plants (Haplophyllum tuberculatum (H) and Sonchus oleraceus L.(S)) was tested against three cell lines: HeLa uterus (H2), A431 skin (A2), and MCF breast (M2) using the MTT assay and the flow cytometric technique in vitro. RESULTS:The results revealed that similar yield percentages were obtained. Extract fractions from the first plant HF3 exerted high effects (>75%) on the three cell lines. The aqueous extract of HF3 exhibited significant (P < 0.001) cell growth inhibition activities estimated as (inhibitory concentration 50 in m/mL) of (0.73 ± 0.08, 0.7566 ± 0.12, and 0.65 ± 0.04) on the HeLa, A431, and MCF7 cells, respectively, compared to standard doxorubicin. CONCLUSIONS:The study concluded that similar yield percentages were obtained. Plant H exhibited higher activity, especially in its aqueous extract. Isolation, identification of the active (s) compounds, and determination of the mechanism of action were highly required.
ABSTRACT:In view of the pandemic of coronavirus disease 2019 (COVID-19), there is a need to identify a specific antiviral therapy. We performed this systematic review to assess the efficacy of remdesivir in the treatment of COVID-19. We searched three electronic databases for clinical trials investigating remdesivir for COVID-19 and included this systematic review. Five trials evaluating 13,558 participants were eligible for this study. Remdesivir, as compared to standard care, increases the rate of clinical improvement at 2 weeks (risk ratio: 1.10; 95% confidence interval: 1.04-1.18). Time to clinical recovery was shorter in the remdesivir group than the standard care group. The mortality rate was lower at 2 weeks in the remdesivir group, but no difference was observed at 4 weeks postrandomization. Extending the duration of remdesivir from 5 days to 10 days did not improve efficacy but increased the risk of adverse events. Findings from this systematic review suggested that remdesivir may slightly improve recovery time and rate of clinical improvement.
OBJECTIVE:Cachexia is one of the major chemotherapy-induced adverse effects, characterized by gradual depletion of muscle mass. Currently, there is no specific treatment for cachexia. This study aims to evaluate the role of silymarin in attenuating muscle wasting in a model of cisplatin-induced cachexia. MATERIALS AND METHODS:Female Swiss albino mice were divided into three groups (n = 6) and received the treatment according to their group for 7 days: NC (Normal Control, receiving normal saline), CP (Cisplatin, receiving cisplatin 3 mg/kg i.p.) and SY+CP (Silymarin+Cisplatin, receiving silymarin 100 mg/kg orally two hours before cisplatin 3mg/kg i.p). Body weight, muscle weight, tumor necrosis factor alpha (TNF-α), and GSH levels were measured, and muscle histopathological studies were performed. RESULTS:Silymarin prevented cisplatin-induced damage in the triceps, quadriceps, and gastrocnemius muscles. Cisplatin administration altered tissue architecture and decreased the size and cross-sectional area of all three muscle fibers, which were significantly restored in the silymarin-treated group. Muscle tissue homogenates from the silymarin-treated group exhibited higher levels of reduced glutathione compared to the cisplatin group. The elevated serum TNF-α levels in the cisplatin group were decreased from 183 ± 1.66 pg/mL to 117.40 ± 10.47 pg/mL in the silymarin-treated mice. Tripartite motif-containing 63 (TRIM63), a muscle atrophy marker, was upregulated, and myogenin, a marker of myogenesis, was decreased by cisplatin, and the expression of both markers was reversed upon silymarin treatment. CONCLUSIONS:Silymarin attenuates cisplatin-induced cachexia through TRIM63 suppression, myogenin restoration, and reduced oxidative and inflammatory stress.
OBJECTIVE:Hexarelin is a growth hormone secretagogue receptor type 1a agonist with a potent anti-apoptotic effect. We studied the neuroprotective effect of hexarelin on the survival of retinal ganglion cells (RGCs) in the retina following optic nerve transection (ONT). MATERIALS AND METHODS:Golden hamsters of 8-9 weeks old were used. For 7 days following ONT with one dose of drug, hamsters were injected with single dose of saline, 25 μg/kg, 50 μg/kg, and 100 μg/kg hexarelin daily for 5 days. For 7 days after ONT with two doses of drugs, saline, 100 μg/kg and 150 μg/kg hexarelin were injected twice daily for 5 days. Survival of RGCs was quantified by immunostaining with Tuj1 antibody in retina whole mount. RESULTS:Single daily doses of 25 μg/kg, 50 μg/kg, and 100 μg/kg hexarelin dose dependently and significantly increased the survival of RGC. The survival rates of RGC in saline, 25 μg/kg, 50 μg/kg, and 100 μg/kg hexarelin-treated hamsters were 51.2%, 62.4%, 68.5%, and 74.6%, respectively, in 7 days ONT. Two daily doses of saline, 100 μg/kg and 150 μg/kg hexarelin promoted survivals to 72.9%, 91.4%, and 109.2%, respectively, in 7 days ONT. CONCLUSIONS:Single daily doses of hexarelin dose dependently increased the survival of RGC. Two daily doses of hexarelin increased RGC survival further and 150 μg/kg hexarelin twice daily is optimal for the survival of RGC.
INTRODUCTION:Diabetics have an increased cardiovascular risk. This risk gets exaggerated by lipid abnormalities additionally. Diabetics have an increased propensity to develop dyslipidemia. Diabetic dyslipidemia is a cluster of lipoprotein abnormalities characterized by increased triglyceride and low-density lipoprotein levels, decreased high-density lipoprotein levels. MATERIALS AND METHODS:From the pilot study, a potent dose of saroglitazar and gemfibrozil was selected for this study. In this study, the experimental rats were divided into five groups of six animals in each group. RESULTS:Combination therapy shows a decrease in lipid profile, atherogenic index, histopathological studies of different organs, and insulin levels compared to individual drugs and shows better therapeutic efficacy. CONCLUSION:Hence, the combination of saroglitazar and gemfibrozil has shown a good safety profile and may represent a novel therapeutic agent that will fulfill the unmet needs in T2DM and diabetic dyslipidemia.
