New Frontier on Antimicrobial Therapy: Long-Acting Lipoglycopeptides.

Long-acting lipoglycopeptides (LGPs), such as dalbavancin and oritavancin, are semisynthetic antibiotics known for their strong effectiveness against a wide array of Gram-positive bacteria. This includes Staphylococcus aureus, both methicillin-sensitive (MSSA) and methicillin-resistant (MRSA) strains, coagulase-negative Staphylococci (CoNS), streptococci, and vancomycin-sensitive Enterococcus faecalis. A literature search was conducted on PubMed and on ClinicalTrials.gov to identify articles published until July 2023 investigating the use of oritavancin and dalbavancin in clinical practice. The review included case reports, case series, observational studies, and clinical studies. Although more consistent data are needed, LGPs seem to be a good alternative that may provide a quicker hospital discharge and reduce long-term intravenous access and therapy. This is attributed to their unique pharmacologic and pharmacokinetic characteristics. More quality data (i.e., number of patients treated with clinical success) are needed before clinicians may use these therapies more widely.

Effect of P-glycoprotein on the rat intestinal permeability and metabolism of the BDDCS class 1 drug verapamil.

The Biopharmaceutics Drug Disposition Classification System (BDDCS) predicts intestinal transporter effects to be clinically insignificant following oral dosing for highly soluble and highly permeable/metabolized drugs (class 1 drugs). We investigated the effect of inhibiting P-glycoprotein (P-gp) on the in vitro rat intestinal permeability (Papp) and metabolism of the class 1 drug verapamil. Jejunal segments from Sprague-Dawley rats fasted overnight were mounted in Ussing chambers filled with 10 mL of Krebs-Ringer buffer (KRB). For P-gp inhibition studies, GG918 0.5 µM was added to the KRB solution. The experiment started by the addition of verapamil (1 or 10 µM) to either apical or basolateral sides. Samples from verapamil donor and receiver compartments were collected at 30 s and 0.166, 0.5, 1, 1.83 and 3 h after the start of the experiment. Analysis of verapamil and its major metabolite, norverapamil, in the samples and intracellularly at 3 h was performed by HPLC. The same experiment was repeated with norverapamil 10 µM (verapamil metabolite), digoxin 100 nM (positive control for P-gp activity) and atorvastatin 1 and 10 µM (example of a class 2 drug). For 1 µM verapamil, efflux ratio (B to A Papp/A to B Papp) was 4.6 and markedly decreased by GG918 (efflux ratio = 1.1). For 10 µM verapamil efflux ratio was 4.1 (control) vs 1.8 (GG918), comparable to the change seen for digoxin 100 nM with an efflux ratio of 3.6 (control) vs 1.6 (with GG918) and atorvastatin (efflux ratio of 5.2 and 3.0 for atorvastatin 1.0 and 10 µM, respectively, changed to 1.0 and 0.65 with GG918). The changes observed in the norverapamil 10 µM experiment were also significant, where efflux ratio decreased from 13.5 (control) to 1.5 (GG918). The extraction ratio (ER) of 10 µM verapamil to norverapamil decreased from 0.41 after an apical dose to 0.21 after a basolateral dose, but was unaffected by the incubation with GG918. The results suggest that P-gp inhibition has an effect on class 1 drug verapamil and class 2 drug atorvastatin Papp in the rat intestine. Moreover, a stronger P-gp effect on the Papp of the more polar norverapamil metabolite was observed. Papp changes caused by the P-gp inhibitor GG918 do not affect the extent of verapamil metabolism.

[Strangulated urethral prolapse. Case report]. / Prolapso uretral encarcerado. A propósito de un caso clínico.

OBJECTIVE: We report a case of strangulated urethral prolapse. METHOD/RESULTS: A 62-year-old female patient presents to the emergency department with complaints of a bleeding vaginal mass, pain referred to the vaginal introitus and dysu-ria. After being diagnosed with a strangulated urethral pro-lapse, surgical excision of the prolapsed urethra was performed. Pathologically, vascular proliferation of the angioma-tous type with thrombosis and focal recanolization (Masson) and inclusion of rare muscular fibers were recognized. Her postoperative course was uneventful, without any recurrence or abnormal micturition. CONCLUSION: For the treatment of strangulated urethral prolapse, surgical excision has been widely applied with successful results.

[Bladder adenocarcinoma. Case report]. / Adenocarcinoma vesical. Aportación de un caso clínico.

OBJECTIVE: Primary bladder adenocarcinoma is a rare entity. We performed a review of the literature on this subject and present a clinical case. METHOD/RESULTS: A 74 year old female patient presents to the emergency department with complaints of gross hematúria not accompanied by lower urinary tract symptoms. Diagnostic work-up included renal and bladder ultrasound, cistoscopy and abdomino-pelvic C. T. scan. Metastatic disease was excluded. Trans-urethral resection revealed an invasive adenocarcinoma. A gynaecologic origin was excluded by further gynaecologic examination and an anterior pelvic exanteration was performed. The bladder specimen showed primary bladder adenocarcinoma, pT3aNO. At 6 months of follow-up, the patient does not present disease progression or surgical complications. CONCLUSION: Primary bladder adenocarcinoma is rare. Unlike urothelial carcinoma, it responds poorly to chemotherapy or radiotherapy Radical Cistectomy offer the best chance of long-term survival.

Prolapso uretral encarcerado. A propósito de un caso clínico / Strangulated urethral prolapse. Case report

Objetivo: Presentar un caso clínico de prolapso de la mucosa uretral encarcerado. Métodos/Resultados: Paciente del sexo femenino de 62 años de edad. Acude al Servicio de urgencias por masa vaginal sangrante acompañada de dolor, localizada en el introioto vaginal y disuria. Después del diagnóstico de prolapso de la mucosa uretral encarcerado, se sometió a exéresis quirúrgica del mismo. El examen histológico reveló uretra con proliferación vascular de tipo angiomatoso con trombosis y recanalización focal (Masson) e inclusión de raros fascículos de fibras musculares. El postoperatorio recorre sin incidencias, no recurrencias o problemas miccionales. Conclusión: Para el tratamiento del prolapso uretral encarcerado, la exéresis quirúrgica es el «gold stardard» (AU)

Objective: We report a case of strangulated urethral prolapse. Method/Results: A 62 year old female patient presents to the emergency department with complaints of a bleeding vaginal mass, pain referred to the vaginal introitus and dysuria. After being diagnosed with a strangulated urethral prolapse, surgical excision of the prolapsed urethra was performed. Pathologically, vascular proliferation of the angiomatous type with thrombosis and focal recanalization (Masson) and inclusion of rare muscular fibers were recognized. Her postoperative course was uneventful, without any recurrence or abnormal micturition. Conclusion: For the treatment of strangulated urethral prolapse, surgical excision has been widely applied with successful results (AU)

Adenocarcinoma vesical. Aportación de un caso clínico / Bladder adenocarcinoma. Case report

Objetivo: El adenocarcinoma primario de vejiga es una entidad rara. Realizamos una revisión de la literatura y presentamos un caso clínico. Métodos/Resultados: Se trata de una paciente del sexo femenino de 74 años de edad que acude al servicio de urgencias por hematuria macroscópica, sin otra sinto matología acompañante. Se sometió a varios exámenes auxiliares de diagnóstico, incluyendo ecografía renal y vesical, cistoscopia y TAC abdominal y pélvico. Después de la realización de resección transuretral de pólipo vesical y frente al diagnóstico de adenocarcinoma músculo invasivo, se somete a una evaluación ginecológica completa, excluyendo enfermedad ginecológica. Se procede a exanteración pélvica anterior. El informe anatomo patológico muestra un adenocarcinoma vesical primario, pT3aN0, con ganglios linfáticos regionales negativos. Después de 6 meses de seguimiento, la paciente no presenta complicaciones resultantes de la cirugía o evidencia de evolución de su enfermedad. Conclusión: El Adenocarcinoma vesical primario es una entidad rara. Al contrario del carcinoma urotelial, responde mal a la quimioterapia y radioterapia, por lo que el único tratamiento eficaz es la cirugía radical (AU)

Objective: Primary bladder adenocarcinoma is a rare entity. We performed a review of the literature on this subject and present a clinical case. Method/Results: A 74 year old female patient presents to the emergency department with complaints of gross hematúria not accompanied by lower urinary tract symptoms. Diagnostic work-up included renal and bladder ultrasound, cistoscopy and abdomino-pelvic C.T. scan. Metastatic disease was excluded. Trans-urethral resection revealed an invasive adenocarcinoma. A gynaecologic origin was excluded by further gynaecologic examination and an anterior pelvic exanteration was performed. The bladder specimen showed primary bladder adenocarcinoma, pT3aN0. At 6 months of follow-up, the patient does not present disease progression or surgical complications. Conclusion: Primary bladder adenocarcinoma is rare. Unlike urothelial carcinoma, it responds poorly to chemotherapy or radiotherapy. Radical Cistectomy offer the best chance of long-term survival (AU)

[A rare case of multiple sclerosing hemangiomas of the lung]. / Um caso raro de hemangioma esclerosante múltiplo do pulmão.

Sclerosing hemangioma of the lung is an uncommon benign tumour which usually presents as an asymptomatic solitary nodule. Multiplicity is very rare. The authors describe a case of a 50 year-old asymptomatic woman with multiple nodular lesions involving all the lobes of both lungs, which underwent diagnostic thoracotomy after thorough investigation to exclude extra-pulmonary neoplasia. The biopsies obtained led to the diagnosis of pulmonary sclerosing hemangiomas. This is one of the few cases described with this presentation.

Bioequivalence evaluation of three different oral formulations of ciprofloxacin in healthy volunteers.

Two bioequivalence studies were performed in twenty four healthy male volunteers with the objective of comparing the bioavailability of three different oral formulations of ciprofloxacin as immediate release tablets 250, 500 and 750 mg (test formulations) with a reference formulation at 500 and 750 mg strengths forms. In study 1, the subjects were enrolled in a single-dose, open-label, 3-period, crossover randomised study, designed to compare the bioavailability of two test formulations of ciprofloxacin (A and B) as 250 and 500 mg tablets, compared to the reference formulation (C), as 500 mg tablets. In study 2, the same 24-subjects were included in a single-dose, open-label, 2-period, crossover randomised study, designed to compare the bioavailability of one test formulation of ciprofloxacin (A) as compared to the reference formulation (B), both products as 750 mg tablets. In both studies multiple blood samples were collected over 24 hours post-dosing. One washout period of six days was observed between the periods. Plasma was harvested and assayed for ciprofloxacin using a selective and sensitive high-performance liquid chromatography (HPLC) method with UV detection. The pharmacokinetic parameter values of Cmax and tmax were obtained directly from plasma data, ke was estimated by log-linear regression, and AUC was calculated by trapezoidal rule. Different statistical tests were performed on the basis of untransformed and log-transformed data and the overall residual variance from ANOVA. Assuming the accepted tolerance intervals, a beta-error of 20% and 90% confidence intervals (alpha = 0.10) of all the generally accepted tests (Westlake, Schuirmann test and Wilcoxon-Tukey nonparametric tests) showed that the formulations can be considered as bioequivalent with respect to the extent of absorption, given by the AUC0-infinity and with respect to rate of absorption as assessed by Cmax and tmax.

Comparative bioavailability of two immediate release tablets of enalapril/hydrochlorothiazide in healthy volunteers.

A bioequivalence study of two oral formulations of 20/12.5 mg tablets of enalapril/hydrochlorothiazide was carried out in 20 healthy male volunteers according to a single dose, two-sequence, crossover randomized design. One washout period of nine days was observed between the two periods. Multiple samples were collected over 96 hours post-dosing. Bioavailability was evaluated on the basis of plasma concentrations of enalapril and its main active metabolite, enalaprilat and hydrochlorothiazide. Plasma samples were assayed for enalapril, enalaprilat and hydrochlorothiazide using a selective and sensitive high-performance liquid chromatography method with mass spectrometry detection (LC-MS). The pharmacokinetic parameter values of Cmax and tmax were obtained directly from plasma data, k(e) was estimated by log-linear regression, and AUC was calculated by trapezoidal rule. Different statistical tests were performed on the basis of untransformed and log-transformed data and the overall residual variance from ANOVA. Assuming the accepted tolerance intervals, a beta-error of 20% and 90% confidence intervals (alpha = 0.10), all the generally accepted tests (Schuirmann test and Wilcoxon-Tukey and Hauschke nonparametric tests) showed that the formulations can be considered as bioequivalent with respect to the extent of absorption, given by the AUC(0-infinity) and with respect to rate of absorption as assessed by Cmax and tmax.