Kalkitoxin attenuates calcification of vascular smooth muscle cells via RUNX-2 signaling pathways

Background@#Kalkitoxin (KT) is an active lipopeptide isolated from the cyanobacterium Lyngbya majuscula found in the bed of the coral reef. Although KT suppresses cell division and inflammation, KT’s mechanism of action in vascular smooth muscle cells (VSMCs) is unidentified. Therefore, our main aim was to investigate the impact of KT on vascular calcification for the treatment of cardiovascular disease. @*Objectives@#Using diverse calcification media, we studied the effect of KT on VSMC calcification and the underlying mechanism of this effect. @*Methods@#VSMC was isolated from the 6 weeks ICR mice. Then VSMCs were treated with different concentrations of KT to check the cell viability. Alizarin red and von Kossa staining were carried out to examine the calcium deposition on VSMC. Thoracic aorta of 6 weeks mice were taken and treated with different concentrations of KT, and H and E staining was performed. Real-time polymerase chain reaction and western blot were performed to examine KT’s effect on VSMC mineralization. Calcium deposition on VSMC was examined with a calcium deposition quantification kit. @*Results@#Calcium deposition, Alizarin red, and von Kossa staining revealed that KT reduced inorganic phosphate-induced calcification phenotypes. KT also reduced Ca++ -induced calcification by inhibiting genes that regulate osteoblast differentiation, such as runtrelated transcription factor 2 (RUNX-2), SMAD family member 4, osterix, collagen 1α, and osteopontin. Also, KT repressed Ca2+ -induced bone morphogenetic protein 2, RUNX-2, collagen 1α, osteoprotegerin, and smooth muscle actin protein expression. Likewise, Alizarin red and von Kossa staining showed that KT markedly decreased the calcification of ex vivo ring formation in the mouse thoracic aorta. @*Conclusions@#This experiment demonstrated that KT decreases vascular calcification and may be developed as a new therapeutic treatment for vascular calcification and arteriosclerosis.

A Randomized Double-Blind Comparative Study of Efficacy and Safety Between Low-Dose Etoricoxib and Ibuprofen Coadministered with Low-Dose Paracetamol for Dental Pain

Objective: To study the safety and efficacy of low-dose etoricoxib and low-dose paracetamol versus ibuprofen and low-dose paracetamol treatments in patients who experienced acute pain after tooth extraction. Methods: A total of 80 patients were recruited and randomized to two study groups, i.e., EP and IP. Group EP received etoricoxib 30 mg once a day and add-on paracetamol 325 mg eight-hourly, and Group IP received ibuprofen 400 mg and paracetamol 325 mg eight-hourly for three days. The analgesic efficacy was assessed by a visual analog scale, pain relief score, and global evaluation score. Patients were assessed at 0, 6, 24, 48, and 72 h. Safety was assessed by the patient’s estimation of the severity of adverse drug reactions using a 3-point scale and the type of adverse drug reactions reported by the patients after 72 h. Results: Mean pain intensity reduction, mean pain relief score, and global evaluation score all showed better analgesic efficacy results in Group EP as compared to Group IP but were not significant (P > 0.05) at 6, 24, 48, and 72 h, respectively. No patient had reported any serious adverse drug reaction in both the groups. Mild to moderate adverse reactions were reported in 20% cases in the IP group and 10% cases in the EP group; however, the incidence of GIT intolerance was seen in 17.5% of the cases in the IP group and none in the EP group. Conclusion: Low-dose etoricoxib with low-dose paracetamol has comparable analgesic efficacy with better safety than therapeutic dose ibuprofen and low-dose paracetamol.

Aster saponin A 2 inhibits osteoclastogenesis through mitogenactivated protein kinase-c-Fos-NFATc1signaling pathway

Background@#In lipopolysaccharide-induced RAW264.7 cells, Aster tartaric (AT) inhibits the nuclear factor kappa-light-chain-enhancer of activated B cells and MAPKs pathways and critical pathways of osteoclast development and bone resorption. @*Objectives@#This study examined how aster saponin A2 (AS-A2) isolated from AT affects the processes and function of osteoclastogenesis induced by receptor activator of nuclear factor kappa-B ligand (RANKL) in RAW264.7 cells and bone marrow macrophages (BMMs). @*Methods@#The cell viability, tartrate-resistant acid phosphatase staining, pit formation assay, polymerase chain reaction, and western blot were carried out to determine the effects of ASA2 on osteoclastogenesis. @*Results@#In RAW264.7 and BMMs, AS-A2 decreased RANKL-initiated osteoclast differentiation in a concentration-dependent manner. In AS-A2-treated cells, the phosphorylation of ERK1/2, JNK, and p38 protein expression were reduced considerably compared to the control cells. In RAW264.7 cells, AS-A2 suppressed the RANKL-induced activation of osteoclast-related genes. During osteoclast differentiation, AS-A2 suppressed the transcriptional and translational expression of NFATc1 and c-Fos. AS-A2 inhibited osteoclast development, reducing the size of the bone resorption pit area. @*Conclusion@#AS-A2 isolated from AT appears to be a viable therapeutic therapy for osteolytic illnesses, such as osteoporosis, Paget’s disease, and osteogenesis imperfecta.

Risk factors responsible for lower respiratory tract infections in children aged under five: a hospital based study

Background: Lower respiratory tract infections (LRTI) contribute significantly in terms of hospital admission and mortality. Along with attempts to improve treatment modalities, it is imperative to identify risk factors that will aid in prevention of these infections.Methods: This was a case-control study done in tertiary care hospital, Cuttack, enrolling inpatients between 2 months to 5 years with symptoms suggestive of LRTI as cases. Those with tuberculosis, aspiration pneumonia, asthma and nosocomial infections were excluded. After obtaining consent, questionnaire was administered to parents, regarding their socio-demographic and other relevant details. Data analysis was done using statistical software Epi Info™, version 6 and association of each variable with LRTI assessed with chi-square test.Results: A total of 314 children were enrolled in the study, with 158 being cases. The case-fatality rate was 23% and 53.8% suffered from complications, the most common being respiratory failure. A significant association was seen between LRTI and social variables namely maternal literacy(p-value<0.005), socioeconomic status (p-value<0.001) and number of children (p-value<0.001), housing pattern (p-value<0.001), fuel used at home (p-value=0.003), ventilation adequacy (p-value=0.004), presence of separate kitchen at home (p-value=0.0009) and presence of overcrowding (p-value<0.001) and individual factors improper breastfeeding(p-value<0.005) and weaning(p-value=0.03), malnutrition (p-value<0.001), vitamin A deficiency(p-value=0.03) and history of respiratory infection in mother (p-value=0.025) or siblings(p-value=0.048).Conclusions: The burden of lower respiratory tract infections can be substantially reduced by prevention using the identification of risk factors such as housing patterns, education of parents and improved nutrition of the children, and measures to combat the same, at each level.

Self-medication with antimicrobials in children: a study in tertiary care hospital, Odisha, India

Background: Antimicrobial resistance is emerging as global threat to health, the injudicious use being linked to multiple reasons namely parental misconceptions, easy drug availability and previous experiences.' Children, due to frequent illnesses, are victims of this misuse and more than fifty percent of these drugs are self-medicated by caregivers. This study attempts to assess the trends associated with self-medication with antimicrobials in children and the factors associated with it.Methods: This is a hospital based cross-sectional study, among pediatric outpatients aged 1 month to 14 years, in SCBMCH and SVPPGIP, Cuttack, during March 2019 to September 2019. A structured dichotomous questionnaire was administered to caregivers, including details of socio-demography and antimicrobials self-medicated. A pilot study was done for period of 1 month, and questionnaire accordingly modified. Data was analysed with Chi- square test and percentages, using SPSS 18.Results: Among the 300 patients studied, prevalence of self-medication with antimicrobials was 21%. Most patients self-medicated on pharmacists' advice (44.4%), commonest reason being similar illness previously (41.3%). Fever (31.7%) and cold cough (28.6%) were usual conditions, with Azithromycin being most frequently administered. 54% of cases self-medicating antimicrobials, had errors of dose or duration, with 27% reporting side-effects. Child's age (p=0.042), father's age (p=0.044), mother's age (p=0.002), chronic illness in child (p=0.002) and type of family (p=0.011) were significantly associated with antimicrobial self-medication in children.Conclusions: The high prevalence of self-medication with antimicrobials mandates need to educate parents and enforce laws regarding illegal dispensing of these drugs, to reduce the threat from resistance.

Study of Medicolegal Aspects of Unknown Cases in P.M.C.H., Patna

Introduction: When people die and their bodies are found withno identifying documentation, it is very difficult for the police toestablish their identities. These bodies are labelled as‘unknown/unidentified dead bodies’ (UIDB). The body ispreserved in the mortuary for 72 hours, from the time it isreceived in the mortuary. If no one claims the body after 72hours the police are legally authorized to dispose of the body.The aim of study is to find incidence of unnatural deaths inrelation to the age, sex, pattern of injuries and other parameterof the unknown victims and to ascertain the root cause of alltypes of deaths.Materials and Methods: This prospective study wasconducted in the Department of Forensic Medicine andToxicology, Patna Medical College, Patna, Bihar, Indiabetween August 2012 to September 2014. All the medico legalautopsies of unknown/unidentified bodies during this periodwere included in the study. Information regarding unclaimedbodies with regard to age, sex, cause of death and manner ofdeath was sourced from the autopsy reports and the inquestpapers of the investigating officers.Results: Out of total of 5103 autopsies done 401(7.85%) wereunknown/unidentified dead persons. 342 cases (85.28%) wereof male. Incidence of unknown/unidentified death was mainly inmiddle age group (30-50yrs) (42.64%). 225 (56.10%) deathswere due to accident/injury. Major cause of death due toinjuries were polytrauma. Highest cases were seen in winterseason and lowest in Autumn. 279 cases were untreated and122 hospitalized or treated cases in total unknown cases.Conclusion: Most of the literature available were on theindividual body identification or identification of victims of massdisasters. Unknown bodies comprised 7.85% of the totalautopsy load of the department. The age group 21-40 yearswas responsible for 44.85% of total cases. Accident is animportant cause of morbidity and mortality in the study area.Males are the most affected population; the common agegroup affected is 21–40 years. However, more studies arerecommended to find the actual cause of accidents andprevalence of homelessness and its health-related effects onmorbidity and mortality, which will help in providing health carefacilities to the needy.

Periodontal pathogens in atheromatous plaque.

Background: There has been increasing attention paid in recent years to the possibility that oral bacterial infection, particularly periodontal disease may infl uence the initiation and or progression of systemic diseases. These studies confi rm the observation that heart disease is the most commonly found systemic condition in patients with periodontal disease. Moreover, the literature has also highlighted substantial evidence indicating the presence of Gram-negative periodontal pathogens in atheromatous plaques. Aim: This study intends to investigate the possible association between periodontal health and coronary artery disease by evaluating periodontal status, association between the periodontal plaque and coronary atheromatous plaques for presence of micro-organisms such as, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, and Tannerella forsythia. Materials and methods: A case-control study was designed with seven patients who had undergone coronary endarterectomy for cardiovascular disease and 28 controls. The periodontal examination for cases was performed 1 day before vascular surgery and the controls were clinically examined. The atheromatous plaque sample collected during endarterectomy and the intraoral plaque samples were subjected to polymerase chain reaction for identifi cation of A. actinomycetemcomitans, P. gingivalis, P. intermedia and T. forsythia. Results: The presence of periodontal bacteria DNA in coronary atheromatous plaques and sub-gingival plaque samples of the same patients was confi rmed by this study. CONCLUSION A correlation was established between putative bacteria contributing to atheromatous plaques and species associated with periodontal disease. One particularly important study to be carried out is the investigation of a possible clinically meaningful reduction in coronary heart disease resulting from the prevention or treatment of periodontal disease.

Endoscopic examination of the upper esophagus by withdrawal of endoscope over guide wire.

Upper gastrointestinal (UGI) endoscopy is an important diagnostic modality in evaluation of patients with upper gastrointestinal (GI) disorders. However, lesions located in the cricopharyngeal area and upper esophagus can be missed, as this area may not be well visualized during endoscopy. This study was conducted to study the utility of a new technique of endoscopic examination of the upper esophagus by withdrawal of endoscope over guide wire in diagnosing esophageal disorders. Patients with suspected upper esophageal disorders on history and radiological investigations were assessed using guide wire assisted endoscopic examination during withdrawal of the endoscope. In this technique, endoscope is inserted into the esophagus under vision and thereafter the whole of esophagus, stomach and proximal duodenum is examined. The endoscope is then withdrawn into the mid-esophagus, a guide wire is fed into the biopsy channel, and thereafter inserted into the esophagus. Once guide wire has been advanced into the esophagus, the endoscope is withdrawn gently over the guide wire into esophagus carefully examining for lesions in upper esophagus and cricopharyngeal area. Twenty cases of various abnormalities localized to the upper esophagus were studied. The final diagnosis in these patients was cervical esophageal web (10), post transhiatal esophagectomy leak (4), heterotopic gastric mucosa (3), posttraumatic esophageal perforation (2), and Zenker's diverticulum (1). Intact web was detected in 2 patients and in 8 patients fractured web was seen. Guide wire assisted examination of upper esophagus improved the ability to visualize and characterize these lesions and no complications were encountered as a result of this procedure. Endoscopic examination of the upper esophagus by withdrawal of endoscope over guide wire is safe and effective in diagnosing anatomical abnormalities of the upper esophagus that may be missed or poorly characterized during standard endoscopy.

Enhancement of gastrointestinal absorption of poorly water soluble drugs via lipid based systems.

Development of knowledge on lipids has attracted the scientific community for the effective utilization of the natural and synthetic lipids. Bioavailability of poorly water soluble drugs from gastrointestinal tract (GIT) can be enhanced by formulating the drugs in lipid based formulations. This formulation can increase the dissolution of poorly water soluble drugs, and facilitates the formation of solubilized phases from which absorption may occur. The enhanced solubility of lipophilic drugs from lipid-based systems will not necessarily arise directly from the administered lipid, but most likely from the intra luminal processing to which they are subjected prior to absorption. This review will focus on assessment of lipid-based formulations of drugs with a consideration of how gastrointestinal physiology, the choice of lipids and their formulation attribute and the mode of lipid digestion in the GIT influence the bioavailability of lipophilic drugs.

Microsatellite instability and its correlation with clinicopathological features in a series of thyroid tumors prevalent in iodine deficient areas

Thyroid tumors display diverse spectrum of histopathological groups with geographic variation in its prevalence. Influence of iodine deficiency (a major causative factor) in its etiology, prevalence, or aggressiveness is debatable which reflects the existence of various genetic events in pathogenesis. The present study was undertaken to study the role of Microsatellite instability (MSI) or LOH (loss of heterozygosity), an indicator of defective mismatch repair system as a genetic change and to explore it as a prognostic marker in thyroid tumors. Tumor tissues from total thyroidectomy surgical specimens and blood (matched control) of 36 patients from iodine deficient areas (10 benign; 26 malignant) were obtained after their consent. Urinary iodine analysis was done by alkali ash method for which 10 ml of urine was collected from 18 patients before surgery. Genomic DNA, isolated from tumor tissue and blood was amplified by polymerase chain reaction (PCR) using mono and dinucleotide markers - BAT-26, BAT-40, TGF(RII, IGFIIR, hMSH3, BAX, D2S123, D9S283, D9S851 and D18S58. PCR products were analysed on 8% denaturing polyacrylamide gel followed by autoradiography. Of total, 66.6% of tumors [70% (7/10) benign and 65.4% malignant cases (17/26)] showed MSI/LOH. Strong association of MSI/LOH with low iodine (P=0.01) and with AMES risk groups i.e. age (P=0.02), tumor size (P=0.04) and metastases (P=0.002) in thyroid tumors was observed. This may help in predicting the biological behaviour and strengthening the hypothesis that iodine deficiency has influence on MSI in thyroid tumors. Our results further substantiate the risk group classification and help in deciding the treatment modality in particular patient.

Pancreatitis in patients with primary hyperparathyroidism.

Records of patients undergoing parathyroidectomy at our institute in the period 1991-2003 were retrospectively analyzed. Pancreatitis was associated in six of 87 patients (6.8%) with primary hyperparathyroidism (PHPT). Pancreatitis was the presenting symptom in five patients, while it developed postoperatively in one case. All patients with a past history of pancreatitis had suffered two or more attacks. All patients had a history of renal stone disease. Four patients also had overt bone disease with multiple fractures. Parathyroid adenoma (4) or carcinoma (1) was the cause in all patients. All five patients who underwent successful parathyroidectomy had resolution of pancreatitis on conservative management and no further attacks during a mean follow up of 28 months (3-84 months). Surgical exploration for parathyroid adenoma failed in one patient; this patient has had further attacks of pancreatitis. Repeat surgical exploration for parathyroidectomy has been advised. Hyperparathyroidism is a rare but treatable cause of pancreatitis. Parathyroidectomy has a salutary effect on the course of pancreatitis.

The clinical risk index of babies (CRIB) score in India.

OBJECTIVE: To assess the usefulness of clinical risk index of babies (CRIB score) in predicting neonatal mortality in extremely preterm neonates, compared to birth weight and gestation. METHODS: 97 preterm neonates with gestational age less than 31 weeks or birth weight less than or equal to 1500 g were enrolled for the prospective longitudinal study. Relevant neonatal data was recorded. Blood gas analysis results and the maximum and the minimum FiO2 required by babies in first 12 hours of life were noted. Mortality was taken as death while the baby was in nursery. The prediction of mortality by birth weight, gestational age and CRIB score was done using the Logistic model, and expressed as area under the ROC curve. RESULTS: The area under the ROC curve for birth weight, gestational age and CRIB score was almost the same, the areas being 0.829, 0.819 and 0.823 respectively. Hence CRIB score did not fare better than birth weight and gestational age in predicting neonatal mortality. CONCLUSION: The CRIB score did not improve on the ability of birth weight and gestational age to predict neonatal mortality in the study.