Spontaneous urinary bladder perforation as a cause of recurrent, progressive ascites with multiorgan dysfunction syndrome

Spontaneous rupture of the urinary bladder wall is a rare complication that may lead to intraperitoneal accumulation of urine and is mistaken for ascites from other causes. This often leads to repeated and inconclusive diagnostic tests. Here, we report the case of a 60-year-old female, with a past history of cervical cancer, who presented with recurrent episodes of pain abdomen and breathlessness over 1 year period. She was hospitalized multiple times and found to have ascites. Ultrasound and computed tomography scan of the abdomen along with an ascitic fluid analysis were done at each admission, which were inconclusive as to the cause of the ascites. A diagnostic laparoscopy to rule out peritoneal metastases showed perforation of the urinary bladder wall with intraperitoneal urine leakage. Bladder wall repair was done the following which the patient recovered uneventfully

ESBL E. coli Urosepsis Resulting in Endogenous Panophthalmitis Requiring Evisceration of the Eye in a Diabetic Patient

A primary infection in a remote site resulting in vision threatening complications like panophthalmitis in a person who is not immune-compromised is rare. We report a case of endogenous bilateral bacterial endophthalmitis progressing into panophthalmitis in one eye requiring evisceration of that eye. A patient admitted with severe ESBL E. coli urosepsis was effectively treated with source control (bilateral DJ stenting for hydroureteronephrosis) and antibiotics. She was found to have features suggestive of bilateral conjunctivitis which progressed to panophthalmitis possibly due to delay in appropriate diagnosis and treatment. Diagnosis requires a very high index of suspicion if eye involvement is noted in a patient with features of bacteraemia and early intervention could possibly produce better outcomes. To our knowledge, this is the first case of ESBL E. coli urosepsis complicated by microbiologically confirmed panophthalmitis

Fatal cerebral arterial gas embolism after endoscopic retrograde cholangiopancreatography

We report the case of a 50-year-old woman undergoing elective endoscopic retrograde cholangiopancreatography, who developed coma and hemiparesis secondary to severe cerebral artery gas embolism. Despite prompt diagnosis and early hyperbaric oxygen therapy (HBO 2 ) she developed severe cerebral edema and died within 24 h

Synthesis, antimalarial activity, and target binding of dibenzazepine-tethered isoxazolines

Malaria, a complex and deadly parasitic infectious disease, is a huge public health problem in many endemic countries around the globe. The prevailing extensive resistance of malaria parasites to traditional drugs and emergence of resistance to the currently used frontline artemisinin-based chemotherapy calls for the development of new drugs. Towards this objective and since compounds containing the dibenzazepine moiety are effective in treating both gametocyte and asexual stage malaria parasites, including multi drug resistant parasites, a library of dibenzazepine tethered 3,5-disubstituted isoxazolines was synthesised via 1,3-dipolar cycloaddition reaction. An additional diversified group of dibenzazepine derivatives were accessed by Suzuki coupling of one of the above dibenzazepine derivatives with various organoboronic acids. All compounds were structurally characterized and were evaluated for their antimalarial activity. They exhibited good to excellent inhibitory activity against the growth of drugsensitive Plasmodium falciparum 3D7 strain with IC50 values ranging from 0.2 to 7.7 mu M. About 50% of the compounds were either minimally or not toxic to human cell lines. Five of the compounds (6j, 6k, 8c, 8k and 8l) that highly inhibited the parasite growth were further assessed for antimalarial activity using an additional chloroquine-sensitive (D6) and two chloroquine-resistant (W2 and 7G8) P. falciparum strains. These compounds were effective against all four strains (3D7, D6, W2 and 7G8), exhibiting IC50 values of 0.1 to 1.75 mM. The dibenzazepines were identified to target the metalloamino-peptidase of parasites. Molecular docking and dynamics simulation studies were performed to understand the binding mode and binding strengths of the selected compounds with the enzyme. In agreement with their excellent antimalarial activity, the data suggested that the compounds can strongly bind to the active site of the enzyme

A novel 4,6-disubstituted-1,2,4-triazolo-1,3,4-thiadiazole derivative inhibits tumor cell invasion and potentiates the apoptotic effect of TNFα by abrogating NF-κB activation cascade

Condensed-bicyclic 4,6-substituted1,2,4-triazolo-1,3,4-thiadiazole derivatives (CBTT) have been shown to possess a wide spectrum of pharmacological activities. In this study, several novel CBTT derivatives were synthesized and investigated for their possible role as anti-neoplastic agents. The anti-proliferative effect of various CBTT derivatives was analyzed against tumor cell lines by (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) MTT assay. One of the potential CBTT derivative, 5-(3-(2,3-dichlorophenyl)-1,2,4triazolo3,4-b1,3,4thiadiazol-6-yl)flurobenzonitrile (DTTF) was found to be the most potent against cervical cancer SiHa cells and exhibited minimal effect against normal cells. Molecular docking analysis indicated that transcription factor NF-$\kappa$B was one of the potential molecular targets modulated by DTTF. Specifically, the drug blocked the TNF$\alpha$-induced phosphorylation of upstream I$\kappa$B$\alpha$ kinase in a time-dependent manner leading to the suppression of NF-$\kappa$B activation and nuclear translocation. DTTF also potentiated the apoptotic effect of TNF$\alpha$, as well as significantly inhibited migration and invasion of tumor cells. Overall, these findings indicate a potential novel role and mechanism(s) of action of DTTF as an anticancer agent against diverse malignancies