Polydrug use (the use of drugs in combination): A brief review

This brief review provides an overview of this topic; it is not a critical review. Polydrug use is a poorly defined concept; it is taken here to mean the simultaneous use of more than one drug. Data on polydrug use is seldom systematically collected, and the use of alcohol and tobacco in combination with illegal drugs is frequently overlooked. If alcohol and tobacco are included, most users are polydrug users, since these drugs are used by most users of illegal drugs, and many people with alcohol problems also use illegal drugs. Polydrug use has increased; drug availability, cultural context and the 'normalization' of drug use are important factors. Gender and racial differences are observed in the prevalence of polydrug use. Implications for drug prevention include the importance of targeting multiple substance use rather than single substances. Aiming prevention campaigns at younger people and focusing on 'gateway' drugs might be more effective. But polydrug users are diverse, and a variety of strategies (aimed at different types of polydrug users) are necessary. Implications for treatment include the evidence of the greater difficulty that polydrug users have in quitting; they may therefore require additional help. A fuller, systematic, review is required; it is expected that this would recommend the commissioning of additional research on this poorly understood phenomenon.     

Astrocytoma and Schwann cells in coculture

Glial fibrillary acidic protein (GFAP) is the principal intermediate filament protein found in mature astrocytes. Although the exact function of GFAP is poorly understood, it is presumed to stabilize the astrocyte’s cytoskeleton and help in maintaining cell shape. Previous studies from our laboratory have shown that when astrocytes were cocultured with primary Schwann cells (pSCs), astrocytes became hypertrophied and fibrous with intensely positive GFAP staining and segregated Schwann cells (SCs) into pockets. In order to understand the functional role of GFAP in this already established astrocyte-SC coculture model, we generated GFAP-negative cell lines from a GFAP-positive astrocytoma cell line and cocultured both the cell lines with pSCs. Our studies demonstrate that the GFAP-positive cell line put out processes toward the SCs, whereas the GFAP-negative cells did not form processes and the majority of the cells remained round. The most significant and interesting finding of this study, however, is the formation of elaborate processes by SCs when grown in coculture with the astrocytoma cells, unlike SCs cultured alone, which showed their typical bipolar spindle-shaped morphology. The extent of processes did not seem to be dependent on GFAP, since SCs cultured with both the cell lines formed similar processes. This coculture model may be useful in elucidating the factor(s) responsible for the formation of processes by SCs and can be further help in our understanding of the mechanism of morphological transformation of SCs.     

Antileishmanial action of Tephrosia purpurea linn,extract and its fractions against experimental visceral leishmaniasis

Tephrosia purpurea (family: Fabaceae), which is used in traditional remedies for the treatment of febrile attacks, enlargement and obstruction of liver, spleen, and kidney, was found to have significant antileishmanial activity, and has been extensively fractionated to locate the abode of activity. A fraction (F062) obtained from N‐butanol extract of T. purpurea showed consistent antileishmanial activity at 50 mg/ kg × 5 days by oral route against Leishmania donovani infection in hamsters. Activity was further confirmed in a secondary model, i.e., Indian langur monkeys (Presbytis entellus). Thus, the fraction F062 from this plant possesses potential to produce significant antileishmanial activity by oral route without producing any toxic side effects. Drug. Dev. Res. 60:285–293, 2003. © 2003 Wiley‐Liss, Inc.     

Analysis of COVID-19-associated rhino-orbital-cerebral mucormycosis patients in a tertiary care center in Northern India

Purpose:An unprecedented surge has been noted in rhino-orbital-Cerebral mucormycosis (ROCM) in times of current COVID-19 pandemic. The present prospective study aims to evaluate clinico-epidemiological profile, risk factors, management, and outcome of the cases of ROCM that presented to our tertiary care center during the study period from April to June 2021.Methods:All patients were subjected to complete history taking, ophthalmological examination, and imaging studies. The patients were staged and were treated with intravenous liposomal amphotericin B (AMB) and sino-nasal debridement of local necrotic tissue. Transcutaneous retrobulbar AMB (TRAMB), orbital decompression, and exenteration were instituted as indicated. All patients were followed up for a minimum of 6 months before arriving at the final outcome. Statistical analysis was performed.Results:A total of 49 patients presented during the study period, with a mean age of 42.2 years. The major risk factors included uncontrolled diabetes (89.8%), COVID-19 positivity (51.02%), and concurrent steroid use (38.77%). The most common presenting symptom was facial pain/swelling (43.65%), while the most common presenting sign was deterioration in vision (75.51%). Intravenous liposomal AMB was given to all patients along with sino-nasal debridement (85.71%), TRAMB (57.14%), orbital decompression (14.28%), and exenteration (12.24%). Overall, mortality at 6 months was 22.45% (11 patients). Age more than 60 years, intracranial extension, and HbA1c of more than 8.0% were observed to be statistically significant indicators of mortality.Conclusion:Early suspicion and timely diagnosis of mucormycosis at rhino-orbital stage is warranted in order to salvage life as well as visual function. TRAMB may prove as potentially favorable treatment modality in cases with limited orbital involvement.     

Cholesterol-conjugated poly(D,L-lactide)-based micelles as a nanocarrier system for effective delivery of curcumin in cancer therapy

Polymeric micelles have been widely explored preclinically as suitable delivery systems for poorly soluble chemotherapeutic drugs in cancer therapy. The present study reported the development of cholesterol (Ch)-conjugated poly(D,L-Lactide) (PLA)-based polymeric micelles (mPEG–PLA-Ch) for effective encapsulation and delivery of curcumin (CUR) at the tumor site. Cholesterol conjugation dramatically affected the particle size and improved drug loading (DL) and encapsulation efficiency (EE). mPEG–PLA-Ch-CUR showed bigger hydrodynamic diameter (104.6?±?2.1?nm, and 169.3?±?1.52?nm for mPEG–PLA and mPEG–PLA-Ch, respectively) due to increased size of the hydrophobic core. The newly developed polymer exhibited low critical micelles concentration (CMC) (25?μg/mL) which is close to lipid-based polymer, PEG-phosphatidyl ethanolamine (12.5?μg/mL) compared to mPEG–PLA (50?μg/mL). mPEG–PLA-Ch micelles exhibited relatively higher EE (93.74?±?1.6%) and DL (11.86?±?0.8%) compared to mPEG–PLA micelles (EE 91.89?±?1.2% and DL 11.06?±?0.8%). mPEG–PLA-Ch micelles were internalized by the cancer cells effectively and exhibited higher cytotoxicity compared to free CUR in both, murine melanoma (B16F10) and human breast cancer (MDA-MB-231) cells. mPEG–PLA-Ch exhibited satisfactory hemocompatibility indicating their potential for systemic application. Further, mPEG–PLA-Ch-CUR demonstrated higher rate of reduction of tumor volume in B16F10-xenografted tumor-bearing mice compared to free CUR. At the end of 22 days, the tumor reduced to 1.87-fold (627.72?±?0.9?mm³ versus 1174.68?±?1.64?mm³) compared to the treatment with free CUR. In conclusion, the experimental data in vitro and in vivo indicated that the newly developed CUR-mPEG–PLA-Ch micelles may have promising applications in solid tumors.     

Evaluation of hearing loss in tympanic membrane perforation

To evaluate and analyse the hearing loss in tympanic membrane perforation based on size, site and duration of perforation. The material for this study was comprised of 100 patients of either sex and of age 15?years and above selected randomly. Size of tympanic membrane perforation was assessed under microscope using calibrated wire look. Patients were divided into three groups according to size; group I (0-9?mm(2)), Group II (9-30?mm(2)), Group III (≥?30?mm(2)); according to site into anterior and posterior group; according to involvement of malleus into malleolar and non malleolar and according to duration into Group A (<1?year), Group B (1-5?years), Group C (≥?5?years). Hearing loss was measured in each case with pure tone audiometry. Data was analysed statistically using paired t-test. Hearing loss increased as the perforation size increased [I vs. II (t?-?4.23, p??0.05). Hearing loss was more in malleolar perforation (t?-?5.74, p?相似文献   

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.