New spectrophotometric microdetermination of carbapenem antibiotics derivatives in pharmaceutical formulations

AbstractA new sensitive spectrophotometric method was developed to determine three carbapenem antibiotics: imipenem, meropenem and ertapenem. The proposed method was based on the formation of the coloured tris(o-phenanthroline)-iron(II) complex (ferroin) [Phen] or Fe (II)-2,2″-bipyridyl complex [Bip] in the reaction of the tested drugs with the corresponding iron (III)-complexes in an acetate pH 4 buffer. The formed coloured complexes showed maximum absorbance at 510 and 520nm for [Phen] and [Bip], respectively. The reaction conditions, including the pH, reagent concentration, reaction time, temperature and stability of the formed coloured species, were optimized to achieve the highest sensitivity. Linear calibration curves were obtained in the concentration ranges from 0.2 to 10, 0.5 to 10 and 0.5 to 10μgmL−1 for the aforementioned drugs in the same order. The developed method was successfully applied to determine the investigated carbapenems in their pharmaceutical formulations with average recoveries of 100.8, 99.8 and 99.4% for the Phen method and 98.9, 101.7 and 100.6% for the Bip method for imipenem, meropenem and ertapenem, respectively. A statistical comparison of the results with the reference method showed good concurrence and indicated no significant difference in accuracy or precision

Proximal femoral cortical thickness and medullary canal diameter in soft and hard water regions

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Therapeutic concentrations of antidepressants inhibit pancreatic beta-cell function via mitochondrial complex inhibition

Diabetes mellitus risk is increased by prolonged usage of antidepressants (ADs). Although various mechanisms are suggested for their diabetogenic potential, whether a direct effect of ADs on pancreatic β-cells is involved is unclear. We examined this idea for 3 ADs: paroxetine, clomipramine and, with particular emphasis, fluoxetine, on insulin secretion, mitochondrial function, cellular bioenergetics, KATP channel activity, and caspase activity in murine and human cell-line models of pancreatic β-cells. Metabolic assays showed that these ADs decreased the redox, oxidative respiration, and energetic potential of β-cells in a time and concentration dependent manner, even at a concentration of 100 nM, well within the therapeutic window. These effects were related to inhibition of mitochondrial complex I and III. Consistent with impaired mitochondrial function, lactate output was increased and insulin secretion decreased. Neither fluoxetine, antimycin nor rotenone could reactivate KATP channel activity blocked by glucose unlike the mitochondrial uncoupler, FCCP. Chronic, but not acute, AD increased oxidative stress and activated caspases, 3, 8, and 9. A close agreement was found for the rates of oxidative respiration, lactate output and modulation of KATP channel activity in MIN6 cells with those of primary murine cells; data that supports MIN6 as a valid model to study beta-cell bioenergetics. To conclude, paroxetine, clomipramine and fluoxetine were all cytotoxic at therapeutic concentrations on pancreatic beta-cells; an action suggested to arise by inhibition of mitochondrial bioenergetics, oxidative stress and induction of apoptosis. These actions help explain the diabetogenic potential of these ADs in humans

Postmortem Toxicology Data of Autopsied Cases in the Northern Border Province, Saudi Arabia: A Six-Year Retrospective Study

Autopsy remains the most reliable tool to study mortality causes.This project was conducted to study toxicological findings in relation to gender, age, manners and causes of death among autopsied cases from 2013-2018 in the Northern Border province of Saudi Arabia. All police, hospitals, toxicology laboratory and autopsy reports related to the autopsied cases within the period of the study were revised. Among 908 autopsied cases during the study period, 144 autopsies (15.8%) showed positive toxicological findings (136 males (94.4%) and 8 females (5.4%)). Positive toxicological findings were significantly more common in cases aged 20-40 years (p<0.0001) without a significant gender difference (p=0.116). The commonest toxicological finding was alcohol 55 cases (6.5%) followed by cannabis in 27 cases (2.9%), while 19 cases (2.1%) showed carboxylhemoglobin ≥10%. Most deaths with positive toxicological screens (98 cases (68.1%)) were reported to be accidental. Six cases were recorded as carbon monoxide poisoning (COP), 3 cases were recorded as alcohol toxicity, and 2 cases were registered as hypertensive induced brain haemorrhages. Brain haemorrhages and aspiration pneumonia were reported among deaths related to alcohol, while intraventricular brain haemorrhage was the cause of death in amphetamine deaths. Cherry red hypostasis and pulmonary edema were found among COP deaths. In conclusion, positive toxicology data were found in a considerable percent of autopsied cases, and they can contribute directly or indirectly to identifying the cause of death. Hence, toxicological screening is mandatory in all suspected deaths and screening should not be neglected in cases with absent suggestive autopsy findings

Unveiling the therapeutic potential of exogenous β-hydroxybutyrate for chronic colitis in rats: novel insights on autophagy, apoptosis, and pyroptosis

Ulcerative colitis (UC) is a chronic relapsing inflammatory disease of the colorectal area that demonstrates a dramatically increasing incidence worldwide. This study provides novel insights into the capacity of the exogenous β-hydroxybutyrate and ketogenic diet (KD) consumption to alleviate dextran sodium sulfate (DSS)-induced UC in rats. Remarkably, both interventions attenuated disease activity and colon weight-to-length ratio, and improved macro and microstructures of the damaged colon. Importantly, both β-hydroxybutyrate and KD curbed the DSS-induced aberrant NLRP3 inflammasome activation as observed in mRNA and protein expression analysis. Additionally, inhibition of the NLRP3/NGSDMD-mediated pyroptosis was detected in response to both regimens. In parallel, these modalities attenuated caspase-1 and its associated consequences of IL-1β and IL-18 overproduction. They also mitigated apoptosis as indicated by the inactivation of caspase-3. The anti-inflammatory effects of BHB and KD were confirmed by the reported decline in the levels of inflammatory markers including MPO, NFκB, IL-6, and TNF-α. Moreover, these interventions exhibited antioxidative properties by reducing ROS production and improving antioxidative enzymes. Their effectiveness in mitigating UC was also evident in the renovation of normal intestinal epithelial barrier function, as shown by correcting the discrepancies in the levels of tight junction proteins ZO-1, OCLN, and CLDN5. Furthermore, their effects on the intestinal microbiota homeostasis were investigated. In terms of autophagy, exogenous β-hydroxybutyrate upregulated BECN-1 and downregulated p62, which may account for its superiority over KD in attenuating colonic damage. In conclusion, this study provides experimental evidence supporting the potential therapeutic use of β-hydroxybutyrate or β-hydroxybutyrate-boosting regimens in UC

Eozinofilna upala u alergijskom rinitisu i nosnoj polipozi

On histopathological examination, nasal polyps and nasal mucosa in allergic rhinitis show different forms of pseudostratified respiratory epithelium, whereas the dominant characteristic of lamina propria is an eosinophilic infiltration. The aim of this study was to compare interleukin (IL)-5 and eosinophilic cationic protein (ECP) levels in the nasal fluid of 42 patients: 12 with allergic rhinitis and nasal septal deviation, 17 non-atopic patients with nasal polyposis, and 13 atopic nasal polyp patients were enrolled in this cross-sectional study. Nasal secretion samples were collected a few days before surgery. The levels of IL-5 were measured using fl ow cytometry and the ECP using a commercial ELISA kit. In addition, we counted eosinophils in hematoxylin-and-eosin-stained sections of all nasal polyp and all nasal mucosa samples taken from the inferior nasal turbinates during septoplasty. A significantly higher concentration of IL-5 was found in the nasal fluid of atopic patients with nasal polyposis than in non-atopic nasal polyp patients (p=0.025) and patients with allergic rhinitis (p=0.05). ECP was higher in atopic nasal polyp patients than in patients with allergic rhinitis (p<0.0001) and than in non-atopic nasal polyp patients (p<0.0001). Polyp eosinophils were higher in atopic’ than in non-atopic patients (p<0.0001) and higher than in the mucosa of patients with allergic rhinitis (p<0.0001). These however had signifi cantly more mucosal eosinophils than was found in the polyps of non-atopic patients’ (p=0.025). ECP levels in nasal fl uid and eosinophil counts in tissue specimens correlated well in all three groups of patients. Our study has shown that atopic nasal polyp patients have a higher level of eosinophilic inflammation than non-atopic patients with nasal polyps and patients with allergic rhinitis.Na histopatološkim pregledima nosni polipi, kao i nosna sluznica u alergijskom rinitisu pokazuju različite oblike pseudoslojevitog respiracijskog epitela, dok je osnovna karakteristika lamine proprije infiltracija eozinofilima. Cilj ove studije bio je usporediti koncentracije interleukina 5 (IL-5) i eozinofilnoga kationskog proteina (ECP) u nosnome sekretu pacijenata s alergijskim rinitisom, neatopičnih i atopičnih pacijenata s nosnom polipozom, kao i usporediti broj eozinofi la u tkivu nosnih polipa/nosne sluznice ovih pacijenata. Četrdeset dvoje (n=42) pacijenata, 12-ero s alergijskim rinitisom i devijacijom nosnog septuma, 17-ero neatopičnih pacijenata s nosnom polipozom i 13-ero atopičnih pacijenata s nosnom polipozom bilo je uključeno u ovu presječnu studiju. Uzorci nosnog sekreta bili su skupljeni iz nosnih šupljina svih ispitanika nekoliko dana prije kirurškog liječenja. Koncentracije IL-5 mjerene su metodom protočne citometrije, dok su koncentracije ECP mjerene komercijalnim ELISA-kitom. Eozinofi li su brojeni u svim uzorcima tkiva nosnih polipa, kao i u svim uzorcima tkiva sluznice uzetih s donje nosne školjke tijekom septoplastike. Značajno više koncentracije IL-5 izmjerene su u nosnom sekretu atopičnih pacijenata s nosnom polipozom u usporedbi s neatopičnim pacijentima s nosnom polipozom (p=0,025) i pacijentima s alergijskim rinitisom (p=0,05). Naši su rezultati pokazali više koncentracije ECP u atopičnih pacijenata s nosnom polipozom nego u pacijenata s alergijskim rinitisom (p<0,0001) i u usporedbi s nealergičnim pacijentima s nosnom polipozom (p<0,0001). Veći broj eozinofi la izbrojen je u tkivu polipa atopičnih pacijenata nego u tkivu polipa neatopičnih pacijenata (p<0,0001), kao i u sluznici pacijenata s alergijskim rinitisom (p<0,0001). U nosnoj sluznici pacijenata s alergijskim rinitisom našli smo značajno veći broj eozinofila nego u polipima neatopičnih pacijenata s nosnim polipima (p=0,025). Konačno, našli smo pozitivnu korelaciju između nivoa ECP u nosnom sekretu i broja eozinofila u uzorcima tkiva u sve tri skupine ispitanika. Zaključili smo da atopični pacijenti s nosnom polipozom imaju viši stupanj eozinofilne upale u usporedbi s neatopičnim pacijentima s nosnim polipima i s pacijentima s alergijskim rinitisom

Cyclodextrin-based potentiometric sensors for Metformin

-Cyclodextrins ( -CDs) based polyvinylchloride (PVC) electrodes were fabricated and applied for potentiometric determination of Metformin (Mf). Matrix composition optimization was done referring the effect of type and content of -CDs, anionic sites and plasticizer. Electrodes incorporated with 2-hydroxypropyl- -CD as sensing ionophore, sodium tetrakis (4-florophenyl) borate (NaTFPB) as anionic site and o-nitrophenyloctyl ether (o-NPOE) as electrode plasticizer showed the best electroanalytical performances. The fabricated electrodes worked satisfactorily in the concentration range from 10-6 to 10-2 mol L-1 with detection limit reaching 7×10-6 mol L-1 and fast response time of 8 s. The developed sensors possessed improved selectivity and have been successfully applied for the potentiometric determination of Mf in pharmaceutical formulation. Comparison of the obtained results with those provided by reference method revealed adequate accuracy for control assay

The direct production of tri- and hexa-substituted benzenes from ketones under mild conditions

Treatment of aryl methyl ketones with tetrachlorosilane in ethanol gives good yields of 1,3-5-triarylbenzenes. Triannulated benzenes result from cyclopentanone and cyclohexanone