Bee Venom: From Venom to Drug

Insects of the order Hymenoptera have a defensive substance that contains many biologically active compounds. Specifically, venom from honeybees (Apis mellifera) contains many enzymes and peptides that are effective against various diseases. Different research papers stated the possibility of using bee venom (a direct bee sting or in an injectable form) in treating several complications; either in vivo or in vitro. Other reports used the active fractions of bee venom clinically or at labratory scale. Many reports and publications have stated that bee venom and its constituents have multiple biological activities including anti-microbial, anti-protozoan, anti-cancer, anti-inflammatory, and anti-arthritic properties. The present review aims to refer to the use of bee venom itself or its fractions in treating several diseases and counteracting drug toxicities as an alternative protocol of therapy. The updated molecular mechanisms of actions of bee venom and its components are discussed in light of the previous updated publications. The review also summarizes the potential of venom loaded on nanoparticles as a drug delivery vehicle and its molecular mechanisms. Finally, the products of bee venom available in markets are also demonstrated.

Neuroleptic malignant syndrome: clinical expression, complication, course, and atypical clinical picture

Background Neuroleptic malignant syndrome (NMS) is an uncommon and lethal side effect of neuroleptics. The clinical expression of this syndrome is diverse. Even with criteria diagnosis, it is hard to recognize it easily. We report a series of 25 cases of NMS among patients hospitalized in psychiatric service at Oujda for 5 years. We have described the clinical characteristics of NMS in these patients, the treatments received, the management, and the course of this syndrome. Results Most of the patients are hospitalized for psychotic or affective disorders according to the Diagnostic and Statistical Manual of Mental Disorders (DSM V) criteria. 92% of patients received conventional neuroleptic, and half of them were under the injectable form. No patient took long-acting injectable antipsychotics. 36% of patients received neuroleptics for the first time. NMS appeared in the first week after the admission in psychiatric service among 24 patients. The most common clinical and biological signs were muscular rigidity, the elevation of creatine phosphokinase (CPK), and alteration of blood pressure. Other symptoms were found in proportion varied between 24% and 72%. 32% of the patients did not develop complications. One patient developed renal failure. All patients recovered, and no deaths were recorded. Conclusions Early recognition of NMS help to rescue patient. It is necessary to detect this syndrome even in the absence of main signs such as fever.

PRIAPISM AS A COMPLICATION OF PSYCHOPHARMACOTHERAPY

Priapism is a serious complication of psychopharmacotherapy, which can result in erectile dysfunction if there is no timely diagnosis and treatment. Purpose: to study cases of priapism in patients taking psychotropic drugs which were described in the literature. Articles were searched in the Medline database (1969-2020) in English by keywords – priapism and psychotropic drugs. 265 articles were found, most of which were devoted to the use of trazodone (81 articles) and resperidone (50) in patients with mental disorders with the development of priapism. There were cases of such complication associated with taking 12 antipsychotics (six – of the first generation and six – of the second; three – drugs of prolonged action) and 12 antidepressants (from the group of tricyclic, tetracyclic, selective serotonin and dopamine reuptake inhibitors, monoamine oxidase inhibitors, serotonin and norepinephrine reuptake antagonists/inhibitors, selective serotonin reuptake inhibitors), as well as four mood stabilizing agents. The prescribed doses of drugs varied widely. Often these medications were used in various combinations. Priapism most often occurred in the first days (month) of treatment with low doses of drugs. Cases of priapism against the background of psychopharmacotherapy are described not only in adults and elderly men, but also in children starting from the age of two, as well as in women who developed clitorism (female version of priapism). Although priapism is caused by many factors, caution should be exercised when adding other psychotropic drugs to treatment, when increasing their single (daily) dose, passing from the tablet to the injectable form, including appointment of depot drugs, and canceling treatment. Special attention should be paid to patients having episodes of prolonged erections and hematological pathology (hemoglobinopathies and thrombophilias) in their medical history. Priapism is a rare but dangerous complication that requires urgent urological care. This condition can develop when taking almost all psychotropic drugs that have serotoninergic, dopaminergic and alpha-adrenergic antagonistic properties.

Atelocollagen Application in Human Periodontal Tissue Treatment—A Pilot Study

Background: The aim of this study is the clinical observation of gingival tissue condition after atelocollagen injection. Methods: In 18 patients, 97 gingival class I Miller recessions were divided according to recession height, gingival papillae loss and thickness of gingivae. Atelocollagen (Linerase, 100 mg) was injected into keratinized gingivae twice or thrice, at two-week intervals. Results: Statistically significant changes in gingival recession, amount of gingival papillae loss and thickness of gingiva were observed, after both two and three collagen injections. Although the degree (height) of recession decreased and gingival tissue thickness increased with every injection; there was no difference in gingival papillae loss between second and third collagen injections. Conclusions: The injectable form of atelocollagen is a promising material for gingival soft tissue regeneration and stimulation and allows for reduction in the number of procedures and support in a variety of surgical scenarios. This is a pilot study that clinically measures the impact of injected atelocollagen on periodontal tissue biotype, including the thickness of gingivae and gingival papillae regeneration.

The Use of Bisphosphonate-Hydroxyapatite Composite in Bone Augmentation

A good bone augmentation and regeneration depends essentially on the use of a high biomimetic hydroxyapatite, respectively of an osteoclast apoptosis promoting compound. The last one, used in oral or injectable form, leads to different gastrointestinal side effects. We suggested and studied, at non-clinical level, a composite of sodium alendronate linked on a biogene hydroxyapatite. The composite was obtained by putting an aqueous solution of alendronate into a suspension of hydroxyapatite in acetone. By physico-chemical methods the binding of alendronate (ALE) on hydroxyapatite was proved, the content of ALE in the composite being 22%. The patients can benefit from this composite due to a total elimination of gastrointestinal side effects as a consequence of limiting the bioactivity only locally.

Complexes of antitubercular antibiotics with cellulose sulfate acetate

Water-insoluble complexes of antituberculosis antibiotics (AB) kanamycin (CNMC), amikacin (AMCC) and capreomycin (CPRMC), traditionally used parenterally, with cellulose acetate sulphate in the form of sodium salt (Na-SAC) were obtained. The possibility of their immobilization on the activated carbon (AC) to create a tablet form of AB was demonstrated. The composition of the complexes was determined depending on the medium pH and the order of solutions components mixing. It was shown that with decreasing pH from 6 to 1 due to an increase in the number of protonated amine groups in AB molecules, the number of contacts with polymer macromolecules increases and the amount of cellobiosic units in the complex’s composition increases as well: in the case of CNMC and AMCC from one to three and to four in the case of CPRMC. The electrostatic nature of the complexation is confirmed by the corresponding bands’ shifts in the IR spectra: Na-SAC sulfate groups and the antibiotic amino groups. It was established in vitro that the Na-SAC–CNMC complexes and their compositions with activated carbon are not only equivalent, but also have the double activity of the standard (injectable) form of CNMC in the relation to tuberculosis mycobacterium. The resulting compositions can be recommended for in vivo testing as a new form of aminoglycoside antibiotics for oral administration.

A cost variation analysis study of various bisphosphonates preparations available in the Indian market

Background: Osteoporosis is a chronic disease leading to weakened and porous bones which increases the risk of fractures. It is a treatable condition using drugs like bisphosphonates. There is wide variation in the cost among various brands of bisphosphonates in the Indian market, so the objective of the study was to analyse cost of different brands of bisphosphonates.Methods: Cost of both oral and injectable bisphosphonates in the same strength and dosage forms was obtained from CIMS India (January-April 2019). For oral form of the drug, price was calculated per 10 tablets, for injectable form the price per ampoule or vial was calculated and cost ratio, percentage of cost variation was calculated.Results: 15 different formulations of bisphosphonates were analyzed and it was found that cost ratio is found to be highest with 60 mg of pamidronate injection and lowest with 10 mg alendronate tablet, also pamidronate 60 mg injection has highest percentage of cost variation (9632%) and lowest cost variation is seen with 10 mg alendronate (35%). Cost ratio of 11 formulations was found to be very high which was >2 while percentage of cost variation of 11 formulations was found to be more 100.Conclusions: This study concludes that there is wide variation in cost of various brands of bisphosphonates in India. The huge price variation creates unnecessary burden leading on the patients resulting in noncompliance which increases the risk of morbidity and mortality. Therefore, there is an urgent need to regulate the cost of various formulations of bisphosphonates which will reduce the financial burden on the patients.

Creating a tissue-specific microdispersed matrix from a decellularized porcine liver

The main problem with decellularization of liver tissue as a tissue-specific matrix/scaffold in liver bioengineered structures is the need to maximize the preservation of the original three-dimensional structure of the tissue and the main components of its extracellular matrix (ECM) while removing cells and genetic material. The attempts to use the existing protocols for the decellularization of other tissues and organs have been unsuccessful. The aim of the work is to develop a method for creation of tissue-specific microdispersed matrix from decellularized porcine liver (TMM DLp). The protocol for decellularization of porcine liver (Lp) fragments has been developed based on the complex application of chemical (sodium dodecyl sulfate and Triton X-100), biochemical (DNase I), and physical (supercritical CO2) methods for treatment the initial tissue. As a result of the found optimal conditions for decellularization of Lp with subsequent cryomicronization of DLp, the injectable form of the microdispersed tissue-specific matrix was obtained, which represents DLp microparticles with the size of 100-200 microns with the residual amount of DNA no more than 10±1.5 ng/mg (less than 1.0%), with the preservation of the microstructure and basic composition of the liver ECM. According to the assessment of biocompatible properties in vitro, TMM DLp samples meet the criteria of biological safety for cytotoxicity and hemolytic activity.

Justification of the use of non-steroidal anti-inflammatory drugs injectable forms

Treatment of acute intense pain requires the use of strong fast-acting analgesics, such as parenteral forms of non-steroidal anti-inflammatory drugs (NSAIDs). Intravenous and intramuscular (i.m.) NSAIDs administration increases the bioavailability of active substances, allows for analgesic therapy in the presence of restrictions for oral administration, and is predominant in the rate of analgesic action onset versus the latter. When choosing NSAIDs for i.m. administration, the risk of topical post-injection and systemic adverse reactions should be considered. Original meloxicam for i.m. injection is characterized by a favorable risk-benefit ratio and ease of use. In clinical studies, there was no significant increase in creatinine phosphokinase levels, reflecting damage to muscle fibers, after a series of injections of meloxicam i.m. versus other NSAIDs, such as diclofenac and piroxicam. During the search in PubMed, Medline, Google, there was no description of serious topical complications after i.m. administration of meloxicam. In recent years, several large open-label studies have been conducted in Russia demonstrating the efficacy and safety of meloxicam injectable form in acute/subacute non-specific back pain and injuries. The review provides a brief description of the main clinical studies concerning the original meloxicam for i.m. injection.KEYWORDS: NSAIDs, meloxicam, intramuscularly, efficacy, safety.FOR CITATION: Karateev A.E. Justification of the use of non-steroidal anti-inflammatory drugs injectable forms. Russian Medical Inquiry. 2020;4(8):518–524. DOI: 10.32364/2587-6821-2020-4-8-518-524.