Morphometric characteristics of the mucous membrane and the cartilaginous component of the larynx are normal at different times during the experimental opioid effect and during withdrawal

Background. The problem of uncontrolled use of opioid drugs is extremely relevant based on the data of domestic and world statistics which are covered in the scientific literature. That is why the study of indicators of morphometric characteristics of the laryngeal mucosa under opioid exposure under experimental opioid exposure will be of interest to both morphologists and practical otorhinolaryngologists. Objective: To study the morphometric parameters of the laryngeal mucosa in normal at different times of the experimental opioid effect and its cancellation. Methods. The material of the study were sexually mature, outbred rats - males in the amount of 61 animals, weighing 80 - 135 g, aged 4.5 - 7.5 months. Histological specimens were prepared according to conventional methods. All morphometric studies were performed using primary (unedited) photographs taken on a Meiji MT4300 LE microscope, Canon EOS 550D x100 lens. All statistical calculations were performed using RStudio v. 1.2.5042. Results. Throughout the experiment, the change of morphometric parameters of the laryngeal mucosa with signs of wavy growth and decline was clearly observed at all times. More positive was the dynamics of morphometric parameters after the abolition of the opioid analgesic, which hypothetically suggests the process of recovery of the mucosa, even after prolonged administration of the opioid.

Heparin and SARS-CoV-2: Multiple Pathophysiological Links

Low molecular weight heparin, enoxaparin, has been one of most used drugs to fight the SARS-CoV-2 pandemic. Pharmacological properties of heparin recognize its specific ability, as with other oligosaccharides and glycosaminoglycan, to bind several types of viruses during their pass through the extracellular matrix of the respiratory tract, as well as its anticoagulant activity to prevent venous thromboembolism. Antithrombotic actions of enoxaparin have been testified both for inpatients with COVID-19 in regular ward and for inpatients in Intensive Care Units (ICUs). Prophylactic doses seem to be able to prevent venous thromboembolism (VTE) in inpatients in the regular ward, while intermediate or therapeutic doses have been frequently adopted for inpatients with COVID-19 in ICU. On the other hand, although we reported several useful actions of heparin for inpatients with COVID-19, an increased rate of bleeding has been recorded, and it may be related to several conditions such as underlying diseases with increased risks of bleeding, increased doses or prolonged administration of heparin, personal trend to bleed, and so on.

Osteomyelitis in Immunocompromised children and neonates, a case series

Background Osteomyelitis in immunocompromised children can present differently from immunocompetent children and can cause devastating sequelae if treated inadequately. We aim to review the aetiology, clinical profile, treatment and outcomes of immunocompromised children with osteomyelitis. Methods Retrospective review of all immunocompromised children aged < 16 years and neonates admitted with osteomyelitis in our hospital between January 2000 and January 2017, and referred to the Paediatric Infectious Disease Service. Results Fourteen patients were identified. There were 10 boys (71%), and the median age at admission was 70.5 months (inter-quartile range: 12.3–135.0 months). Causal organisms included, two were Staphylococcus aureus, two were Mycobacterium bovis (BCG), and one each was Mycobacterium tuberculosis, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Burkholderia pseudomallei and Rhizopus sp. One patient had both Clostridium tertium and Clostridium difficile isolated. Treatment involved appropriate antimicrobials for a duration ranging from 6 weeks to 1 year, and surgery in 11 patients (79%). Wherever possible, the patients received treatment for their underlying immunodeficiency. For outcomes, only three patients (21%) recovered completely. Five patients (36%) had poor bone growth, one patient had recurrent discharge from the bone and one patient had palliative care for underlying osteosarcoma. Conclusions Although uncommon, osteomyelitis in immunocompromised children and neonates can be caused by unusual pathogens, and can occur with devastating effects. Treatment involves prolonged administration of antibiotics and surgery. Immune recovery also seems to be an important factor in bone healing.

Reversible infertility in male dog following prolonged treatment of Malassezia dermatitis with ketoconazole

Background Ketoconazole, an antifungal agent, adversely affects spermatogenesis in rodents, but knowledge on adverse effects of prolonged administration of ketoconazole on the fertility of male dogs is lacking. A case of reversible infertility with azoospermia in a male American Staffordshire terrier treated with ketoconazole is reported here. Case presentation A seven-year old male American Staffordshire terrier treated for 3 months with ketoconazole for a persistent Malassezia dermatitis displayed reduced libido and mating of 3 bitches had been unsuccessful. The dog was presented at the clinic 40 days after the treatment had been stopped. At first presentation, low libido and complete absence of sperm in the ejaculate (azoospermia) associated with low testosterone level were found. Repeated examinations revealed that sperm quality and testosterone level had restored 100 days after ketoconazole had been withdrawn. Thereafter, the dog successfully mated 2 bitches. Conclusion The treatment with ketoconazole for 3 months may have led to reversible infertility characterized by azoospermia. Therefore, owners of stud dogs should be informed of this risk prior to initiating such treatment and in case of infertility, previous treatment with ketoconazole should be considered as a possible cause.

Continuous fentanyl infusion reduces intra-abdominal pressure, postoperative pain and normalizes lungs’ mechanical changes in newborn with viscera-abdominal disproportion in early post-operative period

We aimed to study the influence of prolonged administration of fentanyl on postoperative pain, intra­ab­dominal pressure and mechanical lungs’ changes that may happen in neonates in early post­operative period. 30 newborns (in the period from January 2017 to May 2021) with gastroschisis were divided into two groups ac­cordingly to the method of analgesia (14 – morphine hydrochloride; 16 – prolonged infusion of fentanyl). Lungs’ mechanical characteristics, effectiveness of post­operative analgesia, abdominal wall relaxation was studied by monitoring of dynamic compliance (Cdyn), pressure and flow­volume loops, capnography. Apprising analgesia sta­tus, we measured hemodynamic, SаO2, blood level of cortizol, C­reactive protein (CRP), glucose, analyzed post­operative pain syndrome using visual analogue scales (VAS). Intra­abdominal pressure (IAP) was controlled by Cron. For statistic analysis we used Student’s t­test. In the group with morphine, thete was the increase of IAP by 11–12 cm H2O, being stable during some period of time, and also variable levels of pain according to VAS, the in­creasing of CRP from 0.8 ± 0.25 mg/dl by 5 mg/dl, cortisol by 674.4 nmol/l, and blood glucosae rate – 7.4 mmol/l. Periods with high traumatic effects and poor analgesia (morphine group) reasoned the increasing IAP, step by step dynamic compliance decreasing in 3.4 times, resistance increasing in 2.42 times and PIP rising till 22 cm H2O. Di­rect correlation between IAP increase and lungs’ mechanical changes took place. The study has demonstrated that prolonged administration of fentanyl prevented high increase of IAP, CRP, levels of glucose and cortizol and changes of VAS data, lungs’ mechanical characteristics.

Endovascular treatment of cerebral venous thrombosis.

The article describes a clinical case of cerebral venous thrombosis involving the deep venous system in a 42-year-old patient suffering from acute lymphoblastic leukemia. As the patient’s condition progressively deteriorated despite anticoagulant therapy, endovascular treatment was attempted. Transvenous thrombectomy and local thrombolysis were performed, which made it possible to achieve only partial recanalization. Further prolonged administration of alteplase into the cerebral sinus through a microcatheter facilitated complete recanalization of the direct and transverse sinuses. The restoration of blood flow was accompanied by regression of neurological deficit. This case is discussed in the context of modern approaches to endovascular treatment of cerebral venous thrombosis.

Prolonged Administration of Rudgea viburnoides (Cham.) Benth. Prevents Impairment of Redox Status, Renal Dysfunction, and Cardiovascular Damage in 2K1C-Hypertensive Rats by Inhibiting ACE Activity and NO-GMPC Pathway Activation

Rudgea viburnoides is widely found in the Brazilian Cerrado, and commonly used in Brazilian folk medicine. In this study, we evaluated the effects of prolonged administration of the aqueous extract from R. viburnoides leaves (AERV) on impaired redox status, renal dysfunction, and cardiovascular damage in 2K1C hypertensive rats, as well as its chemical composition by LC-DAD-MS. Renal hypertension (two kidney, one-clip model) was surgically induced in male Wistar rats and AERV (30, 100 and 300 mg/kg) was administered orally five weeks after surgery for 28 days. Renal function was assessed and urinary electrolytes, pH, and density were measured. Electrocardiography, blood pressure and heart rate were recorded. Cardiac and mesenteric vascular beds were isolated for cardiac morphometry and evaluation of vascular reactivity, and aortic rings were also isolated for measurement of cyclic guanosine monophosphate levels, and the redox status was assessed. Prolonged treatment with AERV preserved urine excretion and electrolyte levels (Na+, K+, Ca2+ and Cl−), reversed electrocardiographic changes, left ventricular hypertrophy and changes in vascular reactivity induced by hypertension, and reduced blood pressure and heart rate. This effect was associated with a positive modulation of tissue redox state, activation of the NO/cGMP pathway, and inhibition of the angiotensin-converting enzyme. Glycosylated iridoids, chlorogenic acids, glycosylated triterpenes, O-glycosylated flavonols, and triterpenoid saponins were annotated. AERV showed no acute toxicity in female Wistar rats. Therefore, AERV treatment reduced the progression of cardiorenal disease in 2K1C hypertensive rats, which can be involved with an important attenuation of oxidative stress, angiotensin-converting enzyme inhibition, and activation of the NO/cGMP pathway.

The Preparation of a Novel Poly(Lactic Acid)-Based Sustained H2S Releasing Microsphere for Rheumatoid Arthritis Alleviation

Rheumatoid arthritis (RA) is a chronic, inflammatory autoimmune disease that mainly erodes joints and surrounding tissues, and if it is not treated in time, it can cause joint deformities and loss of function. S-propargyl-cysteine (SPRC) is an excellent endogenous hydrogen sulfide donor which can relieve the symptoms of RA through the promotion of H2S release via the CSE/H2S pathway in vivo. However, the instant release of H2S in vivo could potentially limit its further clinical use. To solve this problem, in this study, a SPRC-loaded poly(lactic acid) (PLA) microsphere (SPRC@PLA) was prepared, which could release SPRC in vitro in a sustained manner, and further promote sustained in vivo H2S release. Furthermore, its therapeutical effect on RA in rats was also studied. A spherical-like SPRC@PLA was successfully prepared with a diameter of approximately 31.61 μm, yielding rate of 50.66%, loading efficiency of 6.10% and encapsulation efficiency of 52.71%. The SPRC@PLA showed significant prolonged in vitro SPRC release, to 4 days, and additionally, an in vivo H2S release around 3 days could also be observed. In addition, a better therapeutical effect and prolonged administration interval toward RA rats was also observed in the SPRC@PLA group.

Age-related differences in the reactivity of the respiratory division of lungs in rats after administration of magnesium chloride

Introduction. Magnesium is directly involved in the regulation of lung function. However, the effectiveness of various magnesium preparations for activating lung function is not unambiguous. One of the reasons for this may be age-related differences in the nature of structural and functional changes in the lungs in response to the administration of magnesium.Aim. To study the reactivity of the lungs respiratory division of different ages rats to prolonged administration of magnesium chloride.Materials and methods. The experiments were performed on 48 male Wistar rats of 3 and 15 months of age. The experimental animals, in addition to the standard diet, received magnesium chloride at a dose of 50 mg/kg body weight daily for 21 days. At the end of the experiment, lung tissue samples were taken for histomorphological and biochemical studies.Results. At the end of the experiment, 3-month-old rats treated with magnesium chloride showed an increase in the size of the alveoli, a decrease in the relative area of the parenchyma and stroma, and an increase in the relative area of air spaces. A decrease in the thickness of the interalveolar septum and the concentration of oxyproline in the lung tissue of these rats may indicate a decrease in the number of connective tissue elements. In 15- month-old experimental animals, on the contrary, an increase in the relative area of the parenchyma and stroma of the lungs (by 14%), a decrease in the relative area of air spaces (by 12%), and an increase in the concentration of oxyproline in the lungs (by 21%) were observed.Conclusion. Thus, the research results indicate age-related differences in changes in morphological and biochemical parameters characterizing the state of the respiratory division of the lungs with prolonged administration of magnesium chloride. The nature and severity of these changes suggests that in 3-month-old rats magnesium increased lung activity, and in 15-month-old animals, on the contrary, it decreased.