A Review on the Pharmacological Importance of PDE5 and Its Inhibition to Manage Biomedical Conditions

Phosphodiesterase type 5 (PDE5) is a cyclic GMP (cGMP) specific protein. It hydrolyzes the phosphodiesterase linkage and catalyzes the conversion of cGMP to 5’ GMP, which controls different physiological activities of the body. PDE5 is associated with biomedical conditions like neurological disorders, pulmonary arterial hypertension, cardiomyopathy, cancer, erectile dysfunction, and lower urinary tract syndrome. Inhibition of PDE5 has now been proven pharmaceutically effective in a variety of therapeutic conditions. Avanafil, tadalafil, sildenafil, and vardenafil are the most commonly used PDE5 inhibitors (PDE5i) today which are often used for the management of erectile dysfunction, lower urinary tract syndromes, malignancy, and pulmonary arterial hypertension. However, these synthetic PDE5i come with a slew of negative effects. Some of the most common side effects include mild headaches, flushing, dyspepsia, altered color vision, back discomfort, priapism, melanoma, hypotension and dizziness, non-arteritic anterior ischemic optic neuropathy (NAION), and hearing loss. In light of the potential negative effects of this class of medications, there is a lot of room for new, selective PDE5 inhibitors to be discovered. We have found 25 plant botanical compounds effectively inhibiting PDE5 which might be useful in treating a variety of disorders with minimal or no adverse effects.

Dyspnea, Obstruction, Smoking, Exacerbation Index, and Chronic Obstructive Pulmonary Disease Test Score: Correlation in Predicting Outcomes in Patients with Chronic Obstructive Pulmonary Disease Exacerbations

Objectives: Chronic obstructive pulmonary disease (COPD) being a disease with systemic consequences necessitate the use of multidimensional indices for a comprehensive assessment of the disease's impact including the future risk of exacerbations and mortality. To study the role of dyspnea, obstruction, smoking, and exacerbation (DOSE) index as a predictor of future disease severity and its correlation with chronic obstructive pulmonary disease test (CAT) score. Measurements and results: A total of 60 inpatients with COPD exacerbations were followed up for 6 months to record the number of exacerbations of COPD. The DOSE index and CAT score were calculated after stabilization within 48 hours of admission, at 1 week, and again at 6 months. The mean difference between DOSE index score at admission and at 1 week was 1.382 � 0.561 and at admission and at 6 months was 2.15 � 0.988, both being statistically significant (p < 0.001). A high DOSE index score (?4) was associated with a greater risk of 2 or more exacerbations [odds ratio (OR), 12 (3.09�.60) and risk estimate, 3.75 (1.53�17)]. For the prediction of exacerbations, the area under the curve (AUC) was larger for the DOSE index (0.854) than the global initiative for chronic obstructive lung disease (GOLD) stage (0.789), p < 0.001 for both. Furthermore, DOSE index correlated significantly with the CAT score, an established health status measure, at all stages of disease severity; at the onset of exacerbation (r = 0.719, p < 0.001), after stabilization at 1 week (r = 0.736, p < 0.001) and at 6 months (r = 0.884, p < 0.001). Conclusion: The DOSE index is a simple, practical multidimensional grading tool for assessing current symptoms, health status, and future risk in COPD and acts as a guide to disease management as its component items can be modified by interventions. Its correlation with CAT, a well-known score is a novel observation, which further corroborates the validity of the DOSE index.

Megaloblastic anemia in children from Eastern Odisha, India: A clinical and hematological profile analysis

Background: Anemia can have severe implications on the health of children including motor development, behavioral and cognitive development. Furthermore, morbidity from infectious disease is higher in anemic children. Nutritional anemia is a major concern in rural India. Aim and Objective: We aimed to observe the percentage of megaloblastic anemia among the anemic children and their clinical and hematological parameters. Materials and Methods: After obtaining permission from the Institutional Ethics Committee, this cross-sectional study was conducted from September 2018 to August 2021. The setting was a tertiary care hospital in the eastern part of Odisha, India. Children of 1� years of age presenting with anemia were included in the study. Details clinical examination and blood tests namely mean corpuscular volume, red blood cell count, total leucocyte count, and platelet count were carried out from venous blood. Descriptive statistical analyses were conducted in STATA software version 15.1. Results: Among the total 150 anemic patients, the majority (126 [84%]) were in the 11� years of age group followed by 24 (16%) in 6� years of age (P < 0.0001). Girls were more (94 [62.7%]) than boys (56 [37.3%]), P < 0.0001. Anorexia was the most frequently encountered clinical symptom (99.3%) followed by pallor (94%), weakness (86%), fatigue (62%), and hyperpigmentation (37.4%). According to hemoglobin level, 40% were suffering from severe anemia, 38.7% was having moderate, and 21.3% was having mild anemia. The majority (74%) were having both Vitamin B12 and folic acid deficiency followed by 16.7% Vitamin B12, and 9.3% folic acid deficiency. Conclusion: Girls were presenting with megaloblastic anemia more than boys. Majority of them were suffering from both Vitamin B12 and folic acid deficiency. Children suffering from megaloblastic anemia present with anorexia, pallor, weakness, and fatigue. A proper health promotion program may be designed to aware the parents about the prevention of nutritional anemia.

Modulated UV-B radiation invoking cytomorphological and biochemical aspects of a medicinal plant, Bhringraj (Eclipta alba (L.) Hassk.)

Aim: The current experimental work has been designed to study the effect of UV-B exposure on the seedling growth and meiotic consequences of Eclipta alba (L.) Hassk.Methodology: The seedlings were exposed to UV-B radiation for different time durations, i.e., 40, 80, 120 min along with control sets. UV-B irradiated seedlings along with respective controls were sown in the field and young floral buds were fixed in Carnoy’s fixative for 24 hrs and preserved in 90% ethanol for meiotic study. Results: Exposure of UV-B exposure resulted in various chromosomal aberrations like stickiness, laggards, bridges, unorientation, precocious, multivalents etc. Chromosomal stickiness was profound abnormality encountered at shorter duration (40 min) to UV-B exposure. The results revealed that UV-B exposure for shorter duration is quite beneficial to plant as it induces significant cytomorphological and biochemical variations. Interpretation: Shorter exposure to UV-B radiation induced certain beneficial traits in Eclipta alba. Since, Eclipta alba is a medicinally significant plant, hence, it is essential to improve their quantitative and qualitative traits through induced mutagenesis using UV-B radiation to impel the novel characteristics of plant

A partnership model for capacity-building of primary care physicians in evidence-based management of diabetic retinopathy in India

In India, more than 72 million people have diabetes. Diabetic retinopathy (DR), a vision-threatening complication of people with diabetes, is an important cause of avoidable blindness. The delay in the detection of DR is due to lack of awareness and shortage of ophthalmologists trained in the management of DR. With this background, in 2015, we initiated a capacity-building program “Certificate Course in Evidence Based Management of Diabetic Retinopathy (CCDR)” with an objective to build the skills and core competencies of the physicians across India in the management of diabetes and DR. The program has completed four cycles and 578 physicians have been trained. The course elicited an excellent response, which reflects the much-felt need for skill improvement in DR diagnosis and management for physicians in India. This model demonstrates an innovative modality to address DR-related avoidable blindness in a resource-restraint country like India.

Association of Cognitive Impairment and Type 2 Diabetes Mellitus: A Case-Control Study

Introduction: Patients with type 2 diabetes mellitus (T2DM)have cognitive deficits that can be attributed to their disease.Mild cognitive impairment (MCI) is a transitional phasebetween the cognitive decline that is expected due to thenormal aging process and the more disconcerting declineof dementia. This case-control study aimed to explorethe association between type 2 diabetes mellitus and mildcognitive impairment and compare the prevalence of mildcognitive impairment between non-diabetics and type 2diabetics.Material and Methods: 50 patients with T2DM and 50 ageand sex matched non-diabetic controls were selected for thestudy. Demographic data and medical history was collectedby face to face interview following which the Mini-Mentalstate examination (MMSE) and the Montreal CognitiveAssesment (MoCA) were conducted. If either of the screeninginstruments suggested MCI, the patient was then subjectedto an extensive medical examination conducted by qualifiedmedical clinicians blinded to the MMSE and MoCA scoresfor a more detailed diagnosis of MCI. Chi square test wasperformed to determine if T2DM was significantly correlatedwith MCI. Linear regression was performed to determine thestrength of years of illness as a predictor of MMSE and MoCAscore.Results: Chi square test revealed a statistically significantcorrelation between T2DM and MCI. Years of illness wasfound to predict 5% of the variance in MMSE score and 14%of the variance in MoCA score.Conclusion: The study established that mild cognitiveimpairment had a significant statistical association withT2DM

Importance of Conventional Radiography in Diagnosis and Management of Giant Cell Tumour at an unusual location.

Giant cell tumour (GCT) or osteoclastoma of the bone is mostly benign but locally aggressive primary tumour of unknown origin occurring at epiphysis. It is a tumour of long bones and rarely seen in bones of hand and foot. The cases are reported in tarsal and carpal bone but involvement of metatarsal bone is very rare. We present a case of twenty years old female patient with GCT of second metatarsal of left foot. The patient underwent aggressive curettage and filling with bone chips and is on regular follow up.

Radiological diagnosis of Cysticercosis of Breast - An unusual presentation.

Breast cysticercosis manifestation is usually uncommon and only a few cases have been reported in the literature. This manifests in the form of signs and symptoms which normally do not point towards the diagnosis. The radiological modalities always narrow down the gap between the complaints and the diagnosis. We present a case with cysticercus cysts in breast parenchyma as well as in both pectoral muscles which was suspected on ultrasonography (USG) and diagnosed on Magnetic Resonance Imaging (MRI). The patient responded to the medical treatment conservatively thus avoiding excisional biopsy. Follow up and repeat MRI has confirmed the cure of the complaints as well as the disease.

Similarity and Dissimilarity in the ‘Rāga’ System of Hindustani Sastriya Sangeet.

In Indian Music there are twelve notes, but there are large number of Ragas. How it could be possible and what are the things which make it possible; actually we have some minor factors and a strong theory behind this which can make differences in them. This article attempts to find those minor factors.

Ethno-Botanical Studies on Some Indigenous Plants Used by the Bodo Tribes of Udalguri District of Bodoland Territorial Autonomous District Area in Assam, India.

Udalguri district of BTAD (Bodoland Territorial Autonomous District) harbors a large numbers of medicinal plants due to its wide range of habitats. The population pattern also indicate wide range tribal localities mainly. Bodo peoples distributed all over the district. An ethnobotanical survey was carried out in the year 2011-2013 in different Bodo areas to assess the traditionally as well as locally used some medicinal plants for various treatments particularly by the Bodo people in that areas. A total of 16 plants were collected and recorded for their uses in various purposes particularly by the local Bodo people in the Udalguri district are enumerated in this short communication.

Delayed gastric emptying time in adult cerebral falciparum malaria.

Objective: We hypothesize that upper gastrointestinal symptoms in cerebral malaria are due to gastric motor dysfunction. But gastric motility studies in cerebral malaria are scarce. Methods: We determined gastric emptying half-time (GET½) of liquid meals quantitatively by radio isotope scintigraphy in 25 patients of cerebral malaria and 10 healthy controls. Results: GET½ was prolonged (46.5 ± 4.8 min) significantly (p <0.001) in patients of cerebral malaria compared to healthy controls (27.6 ± 5.3 min). Conclusion: Cerebral malaria can cause prolongation of gastric emptying time of liquid foods.

Treatment Seeking in Reproductive Age Women with RTIs/STIs : A Community based Cross-sectional Study.

The socio-cultural and economic contexts in developing countries influence the epidemiology or STls and helps in making them an important public health priority. This study was carried out to explore the health care seeking pathway of the women suffering from RTls/STls. influence or major socio-demographic variables on treatment seeking pattern. This cross sectional study was carried out comprising or eight hundred reproductive age (15-49 years) women selected following a multistage sampling procedure. The information pertaining to health seeking behaviour were collected from them using a pre-designed pretested interview schedule. Quantum of RTls/STls in the study group was estimated and symptomatics were asked specially about time lag between appearance of symptoms and seeking acre; reason for not seeking care; outcome of treatment they have taken if any. Out of total 359 subjects with symptoms of RTls/STls only about one-third (37.3%) had sought treatment. Only a few (4.5%) had sought treatment within 1 month of appearance of symptoms. Considering it to be physiological about half of the subjects (45.3%) did not seek treatment. The treatment seeking pattern was highly associated with the level of education (p=0.000). Reluctance in seeking treatment, delay in its initiation, prelerencc for unqualified practitioners in first consultation and significant association between education and treatment seeking pattern emphasize BCC and service provision for control and prevention of RTls/STls.

Ecological problems of tree species in protected ecosystems of Orissa, India.

The tree layer vegetation of two protected ecosystems i.e. Similipal Biosphere Reserve (SBR) and Bhitarkanika National Park (BNP) of eastern ghat was analysed for structure, composition and diversity. With respect to the tree species composition the two protected ecosystems were differed from each other at the family, genera and species level. About 117 tree species representing 85 genera and 42 families were recorded in SBR. The average number of species per hectare was 32.5. However, a total of 29 tree species representing 22 genera and 16 families were recorded in BNP with an average number of species per hectare of 24.17. Species dominancy of the two protected areas was also different due to their difference in habitat condition. In SBR Shorea robusta was the most dominant species while in BNP Excoecaria agallocha was the most dominant species. Shannon-Wiener species diversity was 3.15 for Similipal and 2.314 for Bhitarkanika indicating that Similipal was highly diverse than Bhitarkanika. In general both the protected ecosystems of Orissa are highly rich in biodiversity and are characteristics of good ecological wealth of eastern ghat. Thus conservation and management practices are essential for the sustainability of their biodiversity.

Bone mineral density in children with steroid-sensitive nephrotic syndrome.

Objective. To observe the influence of prednisolone treatment on bone mineral density (BMD) in children with idiopathic nephrotic syndrome. Methods. Duel-energy X-ray absorptiometry of lumbar spine (L1-L4) was performed on 40 patients (18 first episode and 22 relapsers) of steroid sensitive idiopathic nephrotic syndrome. Results. Patients of first episode and relapsers had comparable values of mean age, weight, height, body mass index, serum calcium, phosphate, spine area, bone mineral content (BMC) and BMD. Relapsing nephrotic syndrome patients received significantly higher mean total cumulative dose of prednisolone in comparison to first episode (p<0.001). The BMD Z-scores were normal in 39 of 40 (97.5%) patients. On regression analysis, it was found that both BMC and BMD did not correlate with cumulative dose of prednisolone, when other co-variants such as age, weight, height and spine area were adjusted. Conclusion. Bone mineral density in steroid sensitive nephrotic syndrome is unaffected by cumulative dose of prednisolone therapy both in first episode as well as relapser group of patients.

Occurrence of organochlorine pesticides residues in Kuano river of eastern Uttar Pradesh.

Organochlorine pesticides residue (isomers of HCH a, b, g and DDT) in Kuano river water at pre-monsoon and post-monsoon period were analyzed for the period June, 2004 to May, 2006 by TLC method. Results indicated that presence of isomers of HCH (a, b, g) and DDT in both the study years even though the usage of both these pesticides is restricted. The higher concentration of pesticide was found in post monsoon. The total concentration of HCH ranges from 0.0002 to 0.020 μg l-1 and 0.0002 to 0.009 μg l-1 and total DDT concentration ranged from 0.0009 to 0.003 μg l-1 and 0.00 to 0.0010 μg l-1 during first and second year of study, respectively. No temporal or spatial distribution pattern was found perhaps due to presence of multiple and aleatory sources. In most of the samples the pesticides residues detected were much higher than drinking water quality standards. It can be inferred that the environment may be considerably degraded by these compounds, providing additional impact to the biota and bringing a potential risk to human health. More detailed Monitoring/studies have to be carried out on different months with a wider spectrum of pesticides to get a clear base line data for the entire location

Molecular basesof â: thalassaemia in the thalassaemic population of Bhopal.

Beta- Thalassaemia is a group of heterogenexus recessive disorders common in many parts of the world and one of a major haemoglobinopathy of wide occurrence in the Indian sub-continent. In is distributed to different degrees in different sub-populations. The treatment of this disorder is quite expensive and counseling seems to be the only way for controlling it. Genetic analysis for Beta – Thalassemia disorder is carried out by Amplification Refractory Mutation System (ARMS) technique. Blood samples of 50 cases of Thalassaimin Were obtained from patient attending Pediatrics OPD of Gandhi Medical College & Delta Pathology laboratory. Bhopal and were tested. Out of seven common â – thalassamia mutation, IVSI [ Intra Venous Sequences] nt 5] nuclentidex] (GT). Deletion 619 bp (basic pair) and Cap +1(AC) were found in population of Bhopal in 39.52%, 16.27%, 18.59% 6.97% respectively. Early detection of thalassaemia is, therefore, important not only from treatment point of view, but also for the prevention by genetic counseling.

Biomolecular changes during in vitro organogenesis of Asteracantha longifolia (L.) Nees--a medicinal herb.

High frequency plant regeneration in A. longifolia (L.) was achieved from leaf explant implanted on MS basal medium supplemented with NAA (0.5 mg/l) + BA (2.0 mg/l) through intervening callus phase. Well-developed shoots (>3cm) were successfully rooted on MS medium supplemented with NAA (0.1 mg/l). Protein and total soluble sugar contents were maximum during organogenesis and multiple shoot induction phase compared with non-organogenic callus and root induction phase. Esterase and catalase activities were maximum during organogenic differentiation, while activities were minimum at non-differentiated callus stages. Peroxidase activities were higher during rhizogenesis. Contradiction to peroxidase activity, acid phosphatase activities were high during organogenesis and declined during rhizogenesis. SDS-PAGE analysis of total soluble proteins revealed expression of non-organogenic callus (97.9 kDa), organogenic callus (77.2, 74.1, 21.9 kDa), multiple shoot induction phase (106.6, 26.9, 11.6 kDa) and root induction phase (15.9 kDa) specific polypeptides. Esterase zymogram revealed one band (Rm 0.204) appeared in both organogenic callus and multiple shoot induction phase. Peroxidase zymogram detected two stage specific bands, one band (Rm 0.42) was specific to root induction phase, while another (Rm 0.761) was specific to multiple shoot induction. Catalase and acid phosphatase zymogram resolved one band (Rm 0.752 and 0.435, respectively) in differentiated stages including both multiple shoot induction phase and root induction phase, but absent in undifferentiated phases.

Correlation of antioxidants and fitness levels in undergraduate medical students.

Fitness is the ability of the organism to maintain the various internal equilibriums as closely as possible to the resting state during strenuous exercise and to restore promptly after exercise. The aim of the present study was to evaluate the fitness and correlate it with anti-oxidant levels of 50 male medical students in the age group of 18 to 25 years. Fitness was assessed by Harvard Step Test. The antioxidant status was assessed by Vitamin C and Vitamin E levels in the blood. Three groups were formed on the basis of fitness score. The mean values of fitness scores were 95.33 +/- 7.66, 68.5 +/- 9.22 and 37 +/- 10.9, in-group A, B and C, respectively. Between the three groups, Vitamin E values were significantly different but not the Vitamin C levels. Thus, it is concluded that Vitamin E levels influence the fitness state of an individual.

Bioactive molecules from amphibian skin: their biological activities with reference to therapeutic potentials for possible drug development.

The amphibian skin contains various bioactive molecules (peptides, proteins, steroids, alkaloids, opiods) that possess potent therapeutic activities like antibacterial, antifungal, antiprotozoal, antidiabetic, antineoplastic, analgesic and sleep inducing properties. Research on amphibian skin derived biomolecules can provide potential clue towards newer drug development to combat various pathophysiological conditions. An overview on the bioactive molecules of various amphibian skins has been discussed.