Synthesis and Structure-Activity Relationships of Vasicine Analogues as Bronchodilatory Agents

The series of vasicine (1) analogues, an alkaloid from Adhatoda vasica Nees., were synthesized with changes in A, B or C rings. Compounds 13-19 were evaluated for in vitro bronchodilatory activity using isolated guinea pig tracheal chain. Compounds 3-8 were also synthesized in good yields using microwave-mediated synthesis under solvent free conditions. Compounds 5 and 8 with seven-member C ring were more active than etofylline and caused 100% relaxation of both the histamine and acetycholine pre-contracted guinea pig tracheal chain. The structure-activity relationship studies showed that the quinazoline and oxo functionalities were essential for activity. The compounds without C ring and instead having aliphatic and phenyl substitutions in B ring showed relaxation against histamine pre-contracted tracheal chain only, 2-methyl substituted analogues, 12 and 13, being most active with 100% relaxation effect.     

Evaluating the Effect of Tideglusib-Loaded Bioactive Glass Nanoparticles as a Potential Dentine Regenerative Material

Dental pulp treatment is the least intrusive procedure currently available for preserving the vitality of the pulp. Several studies are underway to improve the bioactivity of pulp capping materials. Tideglusib isa potent anti-inflammatory, antioxidant, and a regenerative drug developed against Alzheimer’s disease and has been shown to be effective in the treatment of dental cavities. However, its bioactive properties encapsulated within the nanoparticles as a component of pulp capping material are largely unknown. In this study, tideglusib-loaded bioactive glass nanoparticles were synthesized (tideglusib-BgNPs) and mixed at various concentrations into the calcium silicate cement to testits physiomechanical and bioactivitiescompared with biodentine (control). The calcium silicate cement with 10wgt% tideglusib-BgNPs showed comparable physiomechanical properties to that of biodentine. Additionally, the assessment of cytotoxicity and bioactivity (cell proliferation, wound healing, and cell migration assays) showed increased bioactivity in terms of better wound healing, increased proliferation, and better migration of human dental pulp stem cells than biodentine. These findings suggest new opportunities to use tideglusib-BgNPs in pulp therapy.     

Cerebral hemodynamics in children with sickle cell disease in India: An observational cohort study

India has the second highest number of cases of sickle cell disease (SCD) and affects the most socioeconomically disadvantaged communities living in a horizontal belt from Gujarat to Odisha state. Despite high prevalence, information about cerebral hemodynamics among children with SCD in India remains scarcely described.We performed transcranial Doppler (TCD) to assess cerebral hemodynamics among Indian children with SCD and evaluated their association with clinical and hematological parameters.Children aged 3-18years, diagnosed with SCD living in Raipur in Chhattisgarh and Ahmedabad in Gujarat state were recruited. TCD was performed to obtain flow velocities from middle cerebral (MCA), intracranial internal carotid (ICA) and basilar artery. Associations were evaluated between timed-average-mean-maximum velocities (TAMMV) and various clinical and hematological parameters.Our prospective study included 62 consecutive children with known SCD. Mean ± SD age of the study population was 9.8 ± 3.9 years and 31 (50%) were male. Mean ± SD hemoglobin was 8.64 ± 1.34 Gm/dL while the mean HbSS ± SD was 70.25 ± 15.27%. While 6 (9.6%) children had suffered from stroke during previous 2 years, 7 (11%) demonstrated abnormal TAMMV. Higher HbSS level along with history of iron chelation therapy, blood transfusion and/or stroke showed a trend towards having higher TAMMV.Stroke and cerebral hemodynamic alterations are common among Indian children with SCD. Larger studies with detailed neuroimaging and genetic evaluations are needed for better understanding, characterization, risk stratification as well as optimization of the timing of blood transfusion to reduce physical disabilities among Indian children with SCD.     

A case of colouterine fistula managed laparoscopically

Fistulas between the uterus and bowel are rarely reported. We report successful laparoscopic management of a colouterine fistula caused by a foreign body in the uterus. Fistulas between the gastrointestinal tract and the female genital tract are usually found between the vagina and rectum as a result of complications of childbirth or iatrogenic trauma. Communication between the uterus and bowel is rarely reported. We report successful laparoscopic management of an unusual case of colouterine fistula caused by a foreign body in the uterus.     

Complete and incomplete lower motor neuron facial palsy in post-COVID-19 mucormycosis

Purpose:To study facial nerve palsy (FNP) in post-COVID-19-mucormycosis patients and its ocular complications, report different presentations of FNP in such patients, and propose its etiopathogenesis based on presentation and clinico-radiologic localization.Methods:A prospective cohort study was carried out in patients of post-COVID-19-mucormycosis who presented at our tertiary center, over a period of 3 months. Motor and sensory examination of the facial nerve was done to diagnose FNP and localize the lesion clinically. Slit-lamp examination was done for grading corneal involvement. MRI brain, orbit, and paranasal sinuses (PNS) with contrast were studied to find involvement along the facial nerve. It was assessed whether this site of lesion corresponded with clinical localization. Data were analyzed using the percentage of total cases and Fisher’s test.Results:A total of 300 patients with post-COVID-19 mucormycosis were examined, of which 30 (10%) patients were found to have FNP. All were lower motor neuron (LMN) type and were associated with corneal complications. The most common site clinically was distal to the chorda tympani (66.66%) and radiologically was infratemporal (IT) fossa (63.4%). The clinical localization significantly correlated with the radiological findings (P = 0.012). Twenty percent of patients showed incomplete involvement of facial musclesConclusion:FNP was found to be of LMN type. The most common site of insult was IT fossa. There was a good clinico-radiological correspondence of lesions. Isolated lesions were also found along the peripheral nerve course, presenting as incomplete facial palsy. Recognition of FNP in post-COVID-19 mucormycosis, in all its variable forms, is important to manage corneal complications.     

An overview on in situ micronization technique – An emerging novel concept in advanced drug delivery

The use of drug powders containing micronized drug particles has been increasing in several pharmaceutical dosage forms to overcome the dissolution and bioavailability problems. Most of the newly developed drugs are poorly water soluble which limits dissolution rate and bioavailability. The dissolution rate can be enhanced by micronization of the drug particles. The properties of the micronized drug substance such as particle size, size distribution, shape, surface properties, and agglomeration behaviour and powder flow are affected by the type of micronization technique used. Mechanical communition, spray drying and supercritical fluid (SCF) technology are the most commonly employed techniques for production of micronized drug particles but the characteristics of the resulting drug product cannot be controlled using these techniques. Hence, a newer technique called in situ micronization is developed in order to overcome the limitations associated with the other techniques. This review summarizes the existing knowledge on in situ micronization techniques. The properties of the resulting drug substance obtained by in situ micronization were also compared.     

Acute,sub-acute and general pharmacological evaluation of 5-(3,4-methylenedioxyphenyl)-4-ethyl-2E,4E-pentadienoic acid piperidide (SK-20): A novel drug bioavailability enhancer

An efflux pump inhibitor, SK-20 (5-(3,4-methylenedioxyphenyle)-4 ethyl-2E,4E-pentadienoic acid piperidide), was assessed for its toxicity at three different pharmacological profiles: acute, sub-acute and general pharmacology with pharmacokinetics. In acute study, the SK-20 was found safe up to a dose of 2000 mg/kg (b.wt.); and at sub-acute, dosages of 50 and 100 mg/kg (b.wt.) were found to be safe. However, dosages of 200 mg or above per kg (b.wt.) showed some morphological alterations in cellular architecture of both liver and kidneys in both sexes, viz., mild vascular congestion along with sporadic hemorrhages and infiltration into renal and hepatic parenchyma by mononucleate cell. General pharmacological studies did not result into any alterations in analgesic, convulsions, rectal temperatures and in the rhythm or the rate of the intestinal motility or the secretion of the bile. While the respiratory and the cardiac rate remained normal, the only parameter to show was the blood pressure, which at all the doses tested, showed a tendency toward reduction. Characteristically, the SK-20 at all doses influenced pentobarbital-induced hypnosis positively and negatively to spontaneous motor activity in a dose dependent manner. Pharmacokinetics of SK-20 revealed it to have retention time at 10.2 min and half life 2.47 h.