ABSTRACT
Polycystic Ovary Syndrome (PCOS) is one of the most prevalent endocrine disorder in women of reproductive age characterized by hyperandrogenism (HA). Current treatment options for PCOS are either with adverse effects or ineffective. Saptasaram kashayam (SK), an ayurvedic formulation is often been a safe traditional alternative medicine to improve the PCOS symptoms as well as its pathological development. However, its principle phytoconstituents or underlying mechanisms have not been investigated. In order to achieve this, the current study systematically utilized computational tools, network pharmacology approaches and molecular docking studies. All identified phytoconstituents of SK were screened by QikProp ADME prediction and 47 were selected based on oral bioavailability and drug likeliness scores. Their 3D structures were submitted to three online target fishing webservers PharmMapper, ChemMapper and Swiss Target Prediction which produced 1084 biological targets for SK comprehensively. 350 known PCOS therapeutic targets were retreived as common targets from three different interrogative disease centric bioinformatic platforms DisGeNET, OMIM and GeneCards. Intersection of 1084 biological targets of SK and 350 PCOS therapeutic targets produced, 88 potential therapeutic targets of SK against PCOS. STRING PPI and Compound-Target-Pathway networks were constructed and analysed using Cytoscape software. GO & KEGG pathway enrichment analysis was performed using DAVID database. 15 PCOS therapeutic target proteins were short listed from network analysis report- PIK3CA, PDPK1, AKT1, PIK3R1, STAT3, MAPK1, MAPK3, EGFR, AR, ESR1, ESR2, SHGB, NOS3, F2 & CREBBP. Targets that were likely to be inhibited/modulated by SK for treatment of PCOS were docked against the screened phytoconstituents and their respective standard inhibitors using GLIDE-SP of Schrodinger suite, Maestro version- 13.0. Results showed that Quercetin, Catechin, Boeravinone J, Genistein, Protocatechuic Acid, Gentisic Acid, Xanthoarnol, Luteolin, Boeravinone F, Tyrosine, Kaempferol, Dalbergioidin, etc exhibited good binding affinities when compared to standard drugs and might be responsible for synergistic/additive protective effect of SK against PCOS. Meanwhile PI3K-Akt signaling pathway, Prolactin signaling pathway, AGE-RAG diabetic complications, HIF-1 signaling pathway and Estrogen signaling pathway were found to be involving the hub genes of interest and in this way, they might be intervened during treatment of PCOS by SK. Present study succeeded in identifying the drug like principle phytoconstituents, probable PCOS therapeutic targets and the underlying molecular mechanism of SK apart from providing reliable evidence for therapeutic potential of SK against PCOS. However further validation by in vitro and in vivo investigations is necessary.
ABSTRACT
Polycystic Ovary Syndrome (PCOS) is one of the most prevalent endocrine disorder in women of reproductive age characterized by hyperandrogenism (HA). Current treatment options for PCOS are either with adverse effects or ineffective. Saptasaram kashayam (SK), an ayurvedic formulation is often been a safe traditional alternative medicine to improve the PCOS symptoms as well as its pathological development. However, its principle phytoconstituents or underlying mechanisms have not been investigated. In order to achieve this, the current study systematically utilized computational tools, network pharmacology approaches and molecular docking studies. All identified phytoconstituents of SK were screened by QikProp ADME prediction and 47 were selected based on oral bioavailability and drug likeliness scores. Their 3D structures were submitted to three online target fishing webservers PharmMapper, ChemMapper and Swiss Target Prediction which produced 1084 biological targets for SK comprehensively. 350 known PCOS therapeutic targets were retreived as common targets from three different interrogative disease centric bioinformatic platforms DisGeNET, OMIM and GeneCards. Intersection of 1084 biological targets of SK and 350 PCOS therapeutic targets produced, 88 potential therapeutic targets of SK against PCOS. STRING PPI and Compound-Target-Pathway networks were constructed and analysed using Cytoscape software. GO & KEGG pathway enrichment analysis was performed using DAVID database. 15 PCOS therapeutic target proteins were short listed from network analysis report- PIK3CA, PDPK1, AKT1, PIK3R1, STAT3, MAPK1, MAPK3, EGFR, AR, ESR1, ESR2, SHGB, NOS3, F2 & CREBBP. Targets that were likely to be inhibited/modulated by SK for treatment of PCOS were docked against the screened phytoconstituents and their respective standard inhibitors using GLIDE-SP of Schrodinger suite, Maestro version- 13.0. Results showed that Quercetin, Catechin, Boeravinone J, Genistein, Protocatechuic Acid, Gentisic Acid, Xanthoarnol, Luteolin, Boeravinone F, Tyrosine, Kaempferol, Dalbergioidin, etc exhibited good binding affinities when compared to standard drugs and might be responsible for synergistic/additive protective effect of SK against PCOS. Meanwhile PI3K-Akt signaling pathway, Prolactin signaling pathway, AGE-RAG diabetic complications, HIF-1 signaling pathway and Estrogen signaling pathway were found to be involving the hub genes of interest and in this way, they might be intervened during treatment of PCOS by SK. Present study succeeded in identifying the drug like principle phytoconstituents, probable PCOS therapeutic targets and the underlying molecular mechanism of SK apart from providing reliable evidence for therapeutic potential of SK against PCOS. However further validation by in vitro and in vivo investigations is necessary.
ABSTRACT
Background: Dyslipidemia and hypertension are a major, common and modifiable risk factor for diseases like a stroke; coronary artery disease etc. which are common causes for mortality in India. Dyslipidemia and hypertension are usually found co-exist, which accelerates the process of atherosclerosis.Methods: It is a cross-sectional study conducted on the patients who are newly diagnosed hypertensive visited Medical OPD in Konaseema institute of medical sciences between January 2018 to June 2019. All were investigated for various clinical parameters on lipid profile abnormalities. Results were compared among cases and controls.Results: A total number of patients included in the study were 167,107 are cases and 60 controls. Significant higher levels of total cholesterol, triglycerides, LDL-c and lower levels of HDL-c were observed in hypertensive patients with p-value significant <0.0001.Conclusions: Hypertensive patients have significantly elevated levels of all forms of cholesterol and a higher percentage of individuals in the dyslipidemic state when compared with normotensive patients. Pre-diabetic state significantly increases the total cholesterol in hypertensive patients.
ABSTRACT
Background: Plasmodium falciparum (P. falciparum) causes vital organ dysfunction. The manifestation of severe form of falciparum malaria includes cerebral malaria, acidosis, severe anaemia, renal failure, hypotension, shock, disseminated intravascular coagulation and convulsion. Death rate used to be high. But vivax malaria is not presented in severe form and there is tendency of recurrence. Present study has been designed to compare clinical profile and severity of P. falciparum and Plasmodium vivax (P. vivax) malaria in coastal district of Andhra Pradesh.Methods: Present study is a prospective comparative randomized observational study conducted in the depart of general medicine Rangaraya Medical College, Kakinada, Andhra Pradesh from February 2016 to May 2018. The study population include 260 patients diagnosed to have P. falciparum and P. vivax malaria and being admitted in the general medicine dept. Govt medical college Kakinada randomly selected based on exclusion and inclusion criteria.Results: Out of 172 Falciparum malaria patients’ anaemia was present in 39.53% patient and out of 88 P. vivax patients 43.18% patients have anaemia. Thrombocytopenia was present in 19.76% patients of falciparum malaria and 79.54% of P. vivax. Increased leucocyte count was seen in 29.65% P. falciparum and 4.54% P. vivax patients. Leukopenia was seen in 9.3% P. falciparum and 1.136% P. vivax patient. PT and APTT was increased in 12.79% patients of P. falciparum malaria and 6.8% patients of P. vivax malaria. Liver enzyme was elevated in 27.9% of P. falciparum patients and 47.72% patients of P. vivax patients. Raised serum urea and creatinine, was seen in 18.60% patients of P. falciparum and 18.18% patients of P. vivax malaria. Electrolyte imbalance was also found in both groups.Conclusions: - In present study number of falciparum malaria cases were more than vivax with male predominance. Hepatomegaly was more common falciparum, but splenomegaly was more common in vivax malaria patients. Anaemia and thrombocytopenia were more common in P. vivax malaria patients. Elevated liver enzyme was more common in P. vivax patients but elevated serum urea and creatinine was almost same in both groups. Except hepatic dysfunction all other complication was more in falciparum then vivax infection. Death was only marginally high in falciparum then vivax malaria patients.
ABSTRACT
Background: Hypertension, a major public health concern, affecting 20-25% of the adult population. It is the major risk factor for diseases involving Cardio Vascular (CV) and renalsystem. The World Health Organization (WHO) has estimated that high Blood Pressure (BP) causes 1 in every 8 deaths, making hypertension the third leading killer in the world. The recent emerging trend in the treatment of hypertension is not only based on the pragmatic need to lower BP levels, but also on lowering the CV risk profile, which is largely linked to the presence of the end organ damage.Methods: One hundred patients with hypertension are recruited in this study. The ethics committee of Rangaraya Medical College, Kakinada approved this study and all the participants provided informed consent for all the procedures in the study protocol.Results: Majority of the patients (40%) with EOD have hypertension of >10 years duration. The relative frequency of various end organ damages (CVS: 34%, CNS: 17%, kidney: 12% and eye: 10%) is also high in patients with hypertension of >10 years duration.Conclusions: A significant proportion of hypertensive subjects had documented associated EOD, with LVH being the most prevalent EOD. The above findings emphasize the important role of the primary care clinicians to the early detection, treatment and control of high blood pressure that might help to reducing overall cardiovascular risk.
ABSTRACT
The objective of this present study was to develop and evaluate transdermal films of alfuzosin hydrochloride for controlled release at a predetermined rate over a prolonged period of time and assessment of film forming ability Cordia dichotoma fruit mucilage using alfuzosin as drug of choice. The films of alfuzosin were prepared by solvent evaporation technique. The formulations, from F1 to F3 contain Cordia dichotoma fruit mucilage (CDFM; 8%, 12% and 16%) and the formulations, from F4 to F6 contain CDFM along with sodium alginate (125 mg, 150 mg and 175 mg). Glycerin and propylene glycol were used as plasticizer; span-80 used as permeation enhancer; methyl paraben and propyl paraben were used as preservatives (in case of plant mucilage as polymer) in all the formulations. Fourier transform infra red spectral analysis studies showed that there is no drug polymer incompatibility. The films of alfuzosin were prepared by using different polymers such as C. dichotoma and also in combination with sodium alginate that had shown good results for all the evaluated parameters within the range. In vitro drug release studies had shown that the maximum release of drug was observed for F3 formulation was 91.87 ± 1.34 at 24 hrs and F6 formulation was 99.62 ± 0.14 at 24 hrs. The concentration of CDFM is increased from 8% to 16% that leads to enhancement of dissolution rate. In-vitro drug release studies of optimized formulations, F3 formulation followed first order and F6 formulation followed zero order kinetics. The obtained results were concluded that CDFM have good film forming ability alone and combination with sodium alginate.
ABSTRACT
Se describe una nueva especie de nematodo del género Thynnascaris, obtenida del teleósteo Rachycentron canadus (Linnaeus). Un detallado examen de dicho nematodo ha permitido establecer una nueva especie para encasillarlo. Muestra notables diferencias en relación a otras especies de Thynnascaris conocidas, tanto en lo que respecta a tamaño corporal, largo del apéndice esofágico y ciego intestinal, situación del anillo nervioso y poro excretor, disposición de las papilas labiales, tipo de estriaciones cuticulares, posición de la vulva, disposición de las papilas caudales, como a tamaño de las espículas. La nueva especie ha sido denominada Thynnascaris shyamasundarii