Total synthesis of the Amaryllidaceae alkaloid clivonine

Two syntheses of the Amaryllidaceae alkaloid clivonine (1) are described. Both employ previously reported 7-arylhydrindane 6 as an intermediate but differ in the method employed for subsequent introduction of what becomes the ring-B lactone carbonyl carbon (C7). The synthesis featuring a Bischler–Napieralski reaction for this transformation constitutes the first asymmetric synthesis of natural (+)-clivonine. Crystal structures for compounds (±)-13, (±)-16, (−)-20 and (±)-28 are also reported

A Case of Severe Psychosis Due to Cushing\u27s Syndrome Secondary to Primary Bilateral Macronodular Adrenal Hyperplasia.

Hypercortisolism is a multisystem disorder that results from inappropriate and excessive glucocorticoid secretion and loss of normal feedback mechanisms of the hypothalamic-pituitary axis. It is broadly divided into adrenocorticotropic hormone (ACTH) dependent and ACTH-independent categories. Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a rare cause of ACTH-independent hypercortisolism, accounting for less than 2% of cases. It usually presents as hypertension, metabolic abnormalities, thromboembolic, cardiovascular, or endocrine disorders but rarely as a neuropsychiatric illness. Therefore, a delay in the diagnosis and management of cognitive illnesses substantially increases morbidity in these patients. Herein, we report a case of severe psychosis due to Cushing\u27s syndrome with PBMAH. A 49-year-old male with a past medical history of diabetes and hypertension presented with acute onset of confusion. The patient\u27s uncontrolled hypertension, hypokalemia, metabolic alkalosis, and resistant psychosis to various psychotropic medications raised the suspicion of an underlying metabolic disorder. Further workup revealed an inappropriate suppression of morning (AM) cortisol after administration of dexamethasone and elevated values of serum AM cortisol and 24-hour urinary cortisol, in addition to low ACTH. Computed tomography (CT) of the abdomen and pelvis with intravenous (IV) contrast was performed to evaluate the adrenal gland which showed multiple nonspecific adrenal nodules bilaterally measuring between 3.5 cm - 4.5 cm. The patient was hence diagnosed with hypercortisolism secondary to PBMAH. The patient was treated with ketoconazole after he refused surgery as a treatment option and was noted to have significant improvement in his psychosis within a week, along with improvement of his hypertension, electrolyte abnormalities, and a significant decrease in the 24-hour urine cortisol level. Neuropsychiatric illness is a rare manifestation and an unusual initial presenting symptom of Cushing\u27s syndrome secondary to primary bilateral macronodular adrenal hyperplasia. A delay in diagnosis often subjects these patients to unnecessary psychotropic medications and prolonged psychiatric hospitalizations. Hence, clinicians must be cognizant of this rare entity when making a diagnostic evaluation to prevent subsequent morbidity and mortality

Polystyrene-Supported N-Methylthiourea: A Convenient New Reagent for the Hydrogenolysis of Bicyclic Endoperoxides.

The single-step preparation of a polystyrene-bound N-methylthiourea and its use for the hydrogenolysis of bicyclic endoperoxides is described

Total synthesis of the lycorenine-type amaryllidaceae alkaloid (±)-clivonine via a biomimetic ring-switch from a lycorine-type progenitor

A fully diastereoselective total synthesis of the lycorenine-type Amaryllidaceae alkaloid (±)-clivonine is reported via a route that employs for the first time a biomimetic ring-switch from a lycorine-type progenitor, thereby corroborating experimentally the biogenetic hypothesis first expounded for these compounds by Barton in 1960

Antibody-Based Immunotherapy To Treat and Prevent Infection with Hypervirulent Klebsiella pneumoniae

Hypervirulent Klebsiella pneumoniae (hvKp) strains are predicted to become a major threat in Asia if antibiotic resistance continues to spread. Anticapsular antibodies (Abs) were developed because disseminated infections caused by hvKp are associated with significant morbidity and mortality, even with antibiotic-sensitive strains. K1-serotype polysaccharide capsules (K1-CPS) are expressed by the majority of hvKp strains. In this study, K1-CPS-specific IgG Abs were generated by conjugation of K1-CPS to immunogenic anthrax protective antigen (PA) protein. Opsonophagocytic efficacy was measured in vitro and in vivo by intravital microscopy in murine livers. In vivo protection was tested in murine models, including a novel model for dissemination in hvKp-colonized mice. Protective efficacy of monoclonal antibodies (MAbs) 4C5 (IgG1) and 19A10 (IgG3) was demonstrated both in murine sepsis and pulmonary infection. In hvKp-colonized mice, MAb treatment significantly decreased dissemination of hvKp from the gut to mesenteric lymph nodes and organs. Intravital microscopy confirmed efficient opsonophagocytosis and clearance of bacteria from the liver. In vitro studies demonstrate that MAbs work predominantly by promoting FcR-mediated phagocytosis but also indicate that MAbs enhance the release of neutrophil extracellular traps (NETs). In anticipation of increasing antibiotic resistance, we propose further development of these and other Klebsiella-specific MAbs for therapeutic use

Reduced Cholesterol Levels during Acute Human Babesiosis.

BACKGROUND: Babesiosis, an intra-erythrocytic protozoan disease, is an emerging zoonotic parasitic disease worldwide. Cholesterol levels are correlated with severe infections, such as sepsis and COVID-19, and anecdotal reports suggest that high-density lipoprotein (HDL) cholesterol declines during acute babesiosis. Our aim was to describe the cholesterol levels in patients with acute babesiosis diagnosed in an endemic area in New York, hypothesizing that HDL levels correlate with the severity of infection. METHODS: We reviewed the medical records of adult patients with babesiosis diagnosed by identification of RESULTS: A total of 39 patients with babesiosis had a lipid profile drawn on presentation. The patients were divided into two groups for comparison based on the treating physician\u27s clinical decision: 33 patients who were admitted to the hospital and 8 patients who were evaluated as outpatients. A history of hypertension was more common in admitted patients (37% vs. 17%, CONCLUSION: LDL and HDL levels are significantly reduced during acute babesiosis, suggesting that cholesterol depletion may predict disease severity. Pathogen and host factors may contribute to a reduction in serum cholesterol levels during acute babesiosis

Reduced Cholesterol Levels during Acute Human Babesiosis

Background: Babesiosis, an intra-erythrocytic protozoan disease, is an emerging zoonotic parasitic disease worldwide. Cholesterol levels are correlated with severe infections, such as sepsis and COVID-19, and anecdotal reports suggest that high-density lipoprotein (HDL) cholesterol declines during acute babesiosis. Our aim was to describe the cholesterol levels in patients with acute babesiosis diagnosed in an endemic area in New York, hypothesizing that HDL levels correlate with the severity of infection. Methods: We reviewed the medical records of adult patients with babesiosis diagnosed by identification of Babesia parasites on a thin blood smear and confirmed by polymerase chain reaction from 2013 to 2018, who also had available a lipid profile drawn at the time of clinical presentation. Additional lipid profile levels were considered as “baseline” if they were drawn within 2 months before or after the infection as part of routine care. Results: A total of 39 patients with babesiosis had a lipid profile drawn on presentation. The patients were divided into two groups for comparison based on the treating physician’s clinical decision: 33 patients who were admitted to the hospital and 8 patients who were evaluated as outpatients. A history of hypertension was more common in admitted patients (37% vs. 17%, p = 0.02). The median levels of low-density lipoprotein (LDL) and HDL were significantly reduced in admitted patients compared to non-admitted patients (46 vs. 76 mg/dL, p = 0.04; and 9 vs. 28.5 mg/dL, p = 0.03, respectively). In addition, LDL and HDL levels returned to baseline values following resolution of acute babesiosis. Conclusion: LDL and HDL levels are significantly reduced during acute babesiosis, suggesting that cholesterol depletion may predict disease severity. Pathogen and host factors may contribute to a reduction in serum cholesterol levels during acute babesiosis