Canine leishmaniosis due to Leishmania infantum is a widespread zoonotic disease. Although aminosidine can be an effective treatment, current therapeutic recommendations do not advocate its use, mainly due to concerns regarding the potential nephrotoxicity and ototoxicity of this drug. The aim of this randomized, blinded, controlled study was to evaluate the nephrotoxicity and ototoxicity of aminosidine-allopurinol combination and compare it with that of meglumine antimonate-allopurinol combination in non-azotemic dogs with leishmaniosis. Forty dogs with leishmaniosis were randomly assigned to be treated with either aminosidine at 15 mg/kg, subcutaneously, once daily for 28 days (group A) or with meglumine antimonate at 100 mg/kg, subcutaneously, once daily for 28 days (group B). In addition to either drug, dogs in both groups were administered allopurinol at 10 mg/kg per os twice daily for 2 months. Kidney function was evaluated through measurement of serum creatinine, urea nitrogen, inorganic phosphorus, and cystatin-c concentrations and complete urinalysis, including protein-to-creatinine ratio, at baseline and after 14, 28, and 60 days from the beginning of the treatment. At the same time points, vestibular and auditory functions were evaluated through neurological examination and brainstem auditory evoked response (BAER) recordings of wave I, wave V, inter-wave I-V latencies, and minimum hearing thresholds. None of the dogs developed clinicopathological evidence of kidney disease during the study. Serum creatinine concentration increased >0.3 mg/dl over baseline in 2 dogs in group A and in 5 dogs in group B. Parameters of kidney function were not significantly different or were improved compared to baseline and the only difference between the two groups was the lower concentration of serum creatinine in group A. None of the dogs developed peripheral vestibular syndrome or hearing impairment. At the end of the study, parameters of auditory function were not significantly different or were improved compared to baseline and there were no differences between the two groups. The results of this study show that the nephrotoxicity and ototoxicity of aminosidine, when administered to non-azotemic dogs with leishmaniosis at 15 mg/kg subcutaneously once daily for 28 days along with allopurinol, is minimal and does not differ from that of meglumine antimonate.

Several diseases would benefit from prolonged drug release provided by systems retained in the stomach for extended time periods. Expandable gastroretentive devices are administered in a collapsed configuration enabling swallowing and regain in situ their native shape having larger spatial encumbrance, thus hindering voidance through the wide open pylorus. An expandable system for gastric retention was here proposed relying on the shape memory behavior of pharmaceutical-grade poly(vinyl alcohol). Different original configurations to be recovered upon exposure to aqueous fluids at 37 °C, potentially enabling gastric retention, were conceived. Prototypes containing allopurinol were directly manufactured by fused deposition modeling or shaped by purposely-designed templates from hot melt extruded rods immediately after production. Various temporary shapes, in principle suitable for administration, were programmed by manual deformation of samples by means of specific templates, under defined temperature conditions. In 0.1 N hydrochloric solution at 37 °C, the prototypes recovered their original shape, reaching the desired spatial encumbrance within few minutes. Release from the samples, although of relatively short duration, was independent of the original shape and processing undergone, and was noticeably slowed down by application of Eudragit RS/RL-based coatings.

Purinergic system plays a role in the regulation of many psychological processes, including mood and activity. It consists of P1 receptors, with adenosine as the agonist, and P2 receptors, activated by nucleotides (e.g., adenosine 5'-triphosphate - ATP). Propounded disturbances of uric acid in affective disorders were related to the introduction of lithium for the treatment of these disorders in the 19th and 20th century. At the beginning of the 21st century, new evidence was accumulated concerning a role of uric acid in the pathogenesis and treatment of bipolar disorder (BD). In patients with BD, higher prevalence of gout and increased concentration of uric acid have been found as well as the therapeutic activity of allopurinol, used as an adjunct to mood stabilizers, has been demonstrated in mania. In recent years, the research on the role of the purinergic system in the pathogenesis and treatment of affective disorders and schizophrenia focuses on the role of adenosine (P1) receptors and nucleotide (P2) receptors. Activation of adenosine receptors is related to an antidepressant activity. Alterations of P2 receptors are also significant for the pathogenesis of affective disorders. The role of purinergic system in schizophrenia is related to the effect of adenosine and nucleotide receptors on dopaminergic and glutamatergic neurotransmission. A lot of data indicate that schizophrenia is related to a deficit of adenosine system. Changes in the purinergic system are also significant for psychopathological symptoms of schizophrenia and for the action of antipsychotic drugs.

Introduction: Drug-drug interactions (DDI) between antiretroviral drugs and drugs for the treatment of metabolic disturbances in people living with human immunodeficiency virus (HIV) (PLWH) have represented a problem of paramount importance in the recent times. The problem has been mainly driven by sharing common metabolizing pathways. This problem has classically been worsened by the frequent use of pharmacokinetic boosters to enhance protease inhibitors and some integrase inhibitors plasma levels. These boosters block the metabolizing routes of many antiretroviral drugs. Areas covered: This article focuses on the interactions between antiretroviral drugs and those drugs used to treat metabolic disturbances which frequently appear in people living with human immunodeficiency virus (PLWH). These include drugs for the treatment of dyslipidemia, insulin resistance, and diabetes mellitus, hyperuricemia, and finally, drugs for the treatment of overweight and clinical obesity. To this end, references from PubMed, Embase, or Web of Science, among others, were reviewed. Expert opinion: The advent of safer drugs, in terms of DDI, in the antiretroviral and the metabolic field, has been due to the increased use of non-boosted antiretrovirals and to the use of drugs with divergent metabolizing paths. Besides, learning by the caregivers on how to decrease the potential for DDI and how to manage interactions once they appear, together with the extensive use of online updated DDI databases, has undoubtedly minimized the problem. The foreseeable increase in the burden of HIV-associated comorbidities and their associated treatments anticipates further complexities in the management of DDI in PLWH.

The combination of Alismatis Rhizoma (AR) and Rhizoma Smilacis Glabrae (RSG), as Chinese herb medicine, has been used for their uric acid-lowering effect. However, the effects and mechanism of the combination of the two medicines have not been fully reported. Therefore, to explore the effects of AR-RSG combination decoction on the treatment of chronic hyperuricemia (HUA) in rats as well as the underlying mechanisms, in this study, at the first stage, a long-term HUA rats model was established by gavage of oteracil potassium plus adenine; allopurinol was used as the positive control, and the uric acid-lowering effects of AR or RSG decoction alone with low and high dose were evaluated, respectively. Serum uric acid (UA) and xanthine oxidase (XOD) were determined mainly, and pathological analysis of the kidney and liver was carried out after sacrifice of the animals. And then, at the second stage, four dose groups of AR-RSG combination treatment were investigated in HUA rats. In addition to the indicators measured at the first stage, the expression of urate anion exchanger 1 (URAT1) in rat kidney was determined by immunohistochemistry. We discovered that the UA levels of the model group in both stages were significantly and steadily higher than those of control groups. AR and RSG alone or in combination possess ability to decrease serum UA level of HUA rats, with effects more marked in the combination groups. The uric acid-lowering mechanism of AR-RSG combination may be related to its inhibiting activity of XOD, improving kidney damage and downregulating the expression of URAT1 in kidney.