Dental delivery systems of antimicrobial drugs using chitosan, alginate, dextran, cellulose and other polysaccharides: A review.

Dental caries, periodontal disease, and endodontic disease are major public health concerns worldwide due to their impact on individuals' quality of life. The present problem of dental disorders is the removal of the infection caused by numerous microbes, particularly, bacteria (both aerobes and anaerobes). The most effective method for treating and managing dental diseases appears to be the use of antibiotics or other antimicrobials, which are incorporated in some drug delivery systems. However, due to their insufficient bioavailability, poor availability for gastrointestinal absorption, and pharmacokinetics after administration via the oral route, many pharmaceutical medicines or natural bioactive substances have limited efficacy. During past few decades, a range of polysaccharide-based systems have been widely investigated for dental dug delivery. The polysaccharide-based carrier materials made of chitosan, alginate, dextran, cellulose and other polysaccharides have recently been spotlighted on the recent advancements in preventing, treating and managing dental diseases. The objective of the current review article is to present a brief comprehensive overview of the recent advancements in polysaccharide-based dental drug delivery systems for the delivery of different antimicrobial drugs.

Rapid Sterility Test Systems in the Pharmaceutical Industry: Applying a Structured Approach to Their Evaluation, Validation and Global Implementation.

The current compendial sterility test has a 14-day incubation time and is often the time-limiting step in the Assess and Release Process of pharmaceutical products. There is an ever-increasing number of technologies available on the market that have benefits in addition to faster Time to Result, such as standardization and automation of readout (eliminating analyst subjectivity) and improved data integrity (including eliminating the need for contemporaneous verification of the result by another analyst). Regulators have been encouraging the pharmaceutical industry to adopt these innovative systems; however, it has taken a considerable time before receiving the first approvals from various health authorities (including both the European Medicines Agency and Food and Drug Administration) for the use of an alternative and rapid sterility test for the release of sterile drug product lots. This article describes a systematic 9-step approach to the evaluation, equipment qualification, validation, and deployment of alternative sterility tests that can be applied by pharmaceutical companies wanting to take advantage of the numerous benefits of alternative sterility tests. Two case studies are presented to illustrate the validation and implementation approach, including statistical methods. Although most of the steps toward implementation are aligned, the validation and transfer have been approached differently for each of the case studies because of differences in the chosen technology as well as independent company internal decisions to comply with validation guidelines. However, both case studies show successful implementation of an alternative sterility test for sterile drug products with an ∼50% reduced incubation time.

Invasive Mucormycosis and Aspergillosis Coinfection Associated with Post-COVID-19 Pneumonia in a Tertiary Care Hospital.

Acute invasive fungal rhinosinusitis is a rare infection primarily affecting patients with co-morbidities like immunosuppression and poorly controlled diabetes. Mucormycosis is increasingly being reported in patients with SARS-CoV-2 (COVID-19). However, reports of coinfection of aspergillosis and mucormycosis involving nose, paranasal sinuses, orbit, and brain are rare in literature. We aimed to evaluate the patient demographics, clinical presentation, and management of cases presenting with mixed infection. We carried out retrospective analysis of 12 patients with confirmed diagnosis of mixed invasive fungal infections post-COVID-19 disease out of 70 cases of COVID-19-associated mucormycosis (CAM) presenting to a tertiary-level hospital in North India from May to June 2021. All patients had diabetes mellitus; the mean age was 48 years. The common presenting features were headache, nasal congestion, palatal ulcer, and vision loss accompanied by facial pain and swelling. Two patients developed cerebral abscess during the course of treatment; three patients had concurrent COVID-19 pneumonia. All patients received systemic liposomal amphotericin B and serial surgical debridements. The overall mortality rate was 16.7%. Our study demonstrates that mucormycosis and aspergillosis are angioinvasive mycoses that are clinically and radiologically identical. KOH direct mount of clinical sample showing septate hyphae should be extensively searched for aseptate hyphae after digestion and clearing of the tissue. A high index of suspicion of mixed infection post-COVID-19 and early initiation of liposomal amphotericin B followed by prompt surgical intervention can reduce the overall morbidity and mortality among patients with this condition.

Microbiological Control for Affinity Capture Chromatography Processing: An Industry Perspective.

The purpose of this paper is to provide a summary of a BPOG-led industry survey of the microbiological control aspects of affinity chromatography processing in the biopharmaceutical industry. The document provides a summary of historical microbiological control concerns, coupled with industry-derived best practices, for material, equipment, and storage controls required to mitigate the potential for microbial ingress and contamination of chromatography resin and equipment. These best practice guidelines, which are derived from the members of the BPOG Bioburden Working Group, are intended to assist biopharmaceutical manufacturers to enhance microbial control and monitoring strategies for chromatography systems.

Diagnostic utility of quantitative cytomegalovirus DNA polymerase chain reaction in intestinal biopsies from patients with inflammatory bowel disease.

OBJECTIVES: Diagnostic utility of cytomegalovirus (CMV) DNA quantitative polymerase chain reaction (qPCR) in inflammatory bowel disease (IBD) has not been established. We aimed to compare diagnostic utility of qPCR for CMV in biopsy specimens with blood, serology, and histopathology. MATERIALS AND METHODS: A total of 132 patients were included (92 ulcerative colitis [UC], 9 Crohn's disease, and 31 unclassified IBD). Comparison between CMV IgM, CMV DNA qPCR in biopsy, in blood and histopathology was done. Positive result in any of the test was considered as CMV infection. Various risk factors for CMV association with IBD were analyzed. RESULTS: Confirmed CMV infection was seen in 41 (31.1%) patients. Diagnostic sensitivity of different assays was: DNA in biopsy seen in 37 (90.2%), DNA in blood in 19 (46.3%), CMV IgM in 15 (36.5%), and histopathology in 8 (19.5%). Thirty-two UC cases were further followed up for a median time of 14.0 (R: 3-31) months. They were grouped as group I - biopsy and blood DNA both positive (14, 43.7%), Group II - biopsy positive and blood negative (17, 53.1%), and Group III - biopsy negative but blood positive (1, 3.1%). CMV DNA viral load in Group I was significantly higher (mean: 4.2 ± 1.0 log10 copies/mg) than Group II (mean: 3.2 ± 0.6 copies/mg) and Group III (viral load: 2.69 log10 copies/ml), P < 0.001. Steroid refractoriness was seen more in Group I cases (n = 9) P < 0.001. A cutoff of ≥2.5 log10 copies/mg of DNA in tissue was predictive for steroid refractoriness (AUROC = 0.84). CONCLUSIONS: Quantitation of CMV DNA in intestinal biopsy is a useful diagnostic tool and can predict response to steroid treatment in patients with UC.

Dopamine D3 receptor antagonism inhibits cocaine-seeking and cocaine-enhanced brain reward in rats.

dopamine D3 receptor is preferentially localized to the mesocorticolimbic dopaminergic system and has been hypothesized to play a role in cocaine addiction. To study the involvement of the D3 receptor in brain mechanisms and behaviors commonly assumed to be involved in the addicting properties of cocaine, the potent and selective D3 receptor antagonist trans-N-[4-[2-(6-cyano-1,2,3,4-tetrahydroisoquinolin-2-yl)ethyl] cyclohexyl]-4-quinolininecarboxamide (SB-277011-A) was administered to laboratory rats, and the following measures were assessed: (1) cocaine-enhanced electrical brain-stimulation reward, (2) cocaine-induced conditioned place preference, and (3) cocaine-triggered reinstatement of cocaine seeking behavior. Systemic injections of SB-277011-A were found to (1) block enhancement of electrical brain stimulation reward by cocaine, (2) dose-dependently attenuate cocaine-induced conditioned place preference, and (3) dose-dependently attenuate cocaine-triggered reinstatement of cocaine seeking behavior. Thus, D3 receptor blockade attenuates both the rewarding effects of cocaine and cocaine-induced drug-seeking behavior. These data suggest an important role for D3 receptors in mediating the addictive properties of cocaine and suggest that blockade of dopamine D3 receptors may constitute a new and useful target for prospective pharmacotherapies for cocaine addiction.

Systemic administration of 1R,4S-4-amino-cyclopent-2-ene-carboxylic acid, a reversible inhibitor of GABA transaminase, blocks expression of conditioned place preference to cocaine and nicotine in rats.

We examined the effect of 1R,4S-4-amino-cyclopent-2-ene-carboxylic acid (ACC), a reversible inhibitor of GABA transaminase, on the expression of conditioned place preference response to cocaine and nicotine in rats. Cocaine (20 mg/kg i.p.) and nicotine (0.4 mg/kg s.c.), but not vehicle or 300 mg/kg i.p. of ACC, produced a significant conditioned place preference response. Pretreatment of animals with 300 and 75 mg/kg i.p. of ACC significantly attenuated the expression of the cocaine- and nicotine-induced conditioned place preference responses, respectively. These results are the first to suggest that reversible inhibition of GABA transaminase may be useful in blocking cue-induced relapse to nicotine and cocaine.