Senolytic treatment reverses obesity-mediated senescent cell accumulation in the ovary.

Senescent cells are in a cell cycle arrest state and accumulate with aging and obesity, contributing to a chronic inflammatory state. Treatment with senolytic drugs dasatinib and quercetin (D + Q) can reduce senescent cell burden in several tissues, increasing lifespan. Despite this, there are few reports about senescent cells accumulating in female reproductive tissues. Therefore, the aim of the study was to characterize the ovarian reserve and its relationship with cellular senescence in genetically obese mice (ob/ob). In experiment 1, ob/ob (n = 5) and wild-type (WT) mice (n = 5) at 12 months of age were evaluated. In experiment 2, 2-month-old female ob/ob mice were treated with senolytics (D + Q, n = 6) or placebo (n = 6) during the 4 months. Obese mice had more senescent cells in ovaries, indicated by increased p21 and p16 and lipofuscin staining and macrophage infiltration. Treatment with D + Q significantly reduced senescent cell burden in ovaries of obese mice. Neither obesity nor treatment with D + Q affected the number of ovarian follicles. In conclusion, our data indicate that obesity due to leptin deficiency increases the load of senescent cells in the ovary, which is reduced by treatment by senolytics. However, neither obesity nor D + Q treatment affected the ovarian reserve.

Tandem C(sp3)-H Arylation/Oxidation and Arylation/Allylic Substitution of Isoindolinones.

Isoindolinones comprise an important class of medicinally active compounds. Herein we report a straightforward functionalization of the isoindolinones with aryl bromides (22 examples) using a Pd(OAc)2/NIXANTPHOS-based catalyst system. Additionally 3-aryl 3-hydroxy isoindolinone derivatives, which exhibit anti-tumor activity, can be accessed via a tandem reaction. Thus, when the arylation product is exposed to air under basic conditions, in situ oxidation takes place to install the 3-hydroxyl group. Furthermore, a tandem arylation/allylic substitution reaction is advanced in which both the arylation and allylic substitution are catalyzed by the same palladium catalyst. Finally, a tandem arylation/alkylation procedure is presented. These tandem reactions enable the synthesis of a variety of structurally diverse isoindolinone derivatives from common starting materials.

Palladium-Catalyzed Direct α-Aryation of Benzyl Thioethers with Aryl Bromides.

The arylation of sp3-hybridized C-H's bonds is a powerful strategy to build molecular complexity and diversity. A novel and efficient palladium-catalyzed direct sp3 C-H arylation of aryl and alkyl benzyl thioether derivatives with aryl bromides is reported. The reaction involves reversible deprotonation of the benzylic C-H's of the thioether with either LiN(SiMe3)2 or NaN(SiMe3)2 and subsequent cross-coupling to provide the functionalized products in up to 97% yield. A screen of 24 of the most successful ligands in cross-coupling chemistry led to the identification of NiXantPhos as the only viable ligand for this challenging coupling.

Short-term silver accumulation in tissues of three marine invertebrates: shrimp Penaeus duorarum, sea hare Aplysia californica, and sea urchin Diadema antillarum.

The present study was carried out to examine possible differential silver distribution among several tissues of three marine invertebrate species: the shrimp Penaeus duorarum, the sea hare Aplysia californica, and the sea urchin Diadema antillarum. Animals were exposed to sub-lethal concentrations of silver (1 or 10 microg/L) in seawater for 48 h. In gill-breathing species (shrimp and sea hare), higher silver accumulation in gills were associated with higher hemolymph silver levels. Furthermore, sea urchin showed lower hemolymph silver concentrations than shrimp and sea hare. These findings suggest that gills are an important route for silver uptake in marine invertebrates. In both sea hare and shrimp, hepatopancreas silver accumulation was concentration-dependent and this organ accumulated the most silver after 48 h of exposure, suggesting a possible involvement of the hepatopancreas in both silver accumulation and detoxification in marine invertebrates. In shrimp and sea hare, substantial silver accumulation in nervous tissues was detected, suggesting the need for further studies on possible behavioral effects of silver in these invertebrate species. In sea urchin, egg mass accumulated more silver than other tissues analyzed, indicating the need for future studies on possible reproductive effects of silver in sea urchin. In all three species, the lowest silver concentrations were observed in muscle, suggesting a low potential of this tissue for trophic transfer of silver.

Mechanism of acute silver toxicity in marine invertebrates.

In freshwater crustaceans and in both freshwater and marine fish, the key mechanism of acute silver toxicity involves ionoregulatory impairment. An inhibition of the Na+ ,K+-ATPase located at the basolateral membrane of the gill epithelium seems to be the key site for silver toxicity. However, studies to determine if the same mechanism of toxicity is occurring in marine invertebrates, which also are ionoregulators, had not been done. Thus, the present study was carried out to determine acute silver effects on hemolymph osmo- and ionoregulation in three marine invertebrates: the shrimp Penaeus duorarum, the sea hare Aplysia californica, and the sea urchin Diadema antillarum. Animals were exposed to silver (1 or 10 microg/L), as silver nitrate, in seawater for 48 h. Results show that acute silver exposure did not affect hemolymph osmolality or ion concentration (Na+, Cl-, K+, Ca2+ and Mg2+) in the three species studied. However, silver induced significant changes in the water content in shrimp gill and sea hare gill and hepatopancreas. Silver also caused significant changes in Na+ ,K+-ATPase activity and in both total and intracellular ion (Cl-, Na+, K+, Mg2+, and Ca2+) concentrations in different tissues of the three species studied. Overall, these results show that the key mechanism of acute silver toxicity in marine invertebrates is not associated with an osmotic or ionoregulatory impairment at the hemolymph level, as observed in freshwater fish and crustaceans and in seawater fish. However, they indicate that acute waterborne silver induces significant changes in Na+ ,K(+)-ATPase activity and probably affects other mechanisms involved in water and ion transport at the cell membrane level, inducing impairments in water and ion regulation at the cellular level in different tissues of marine invertebrates. These results indicate the need to consider other "toxic sites" than gills in any future extension of the biotic ligand model (BLM) for seawater.

The epidemiology of prostate cancer in Jamaica

PURPOSE: Before this study, the highest reported incidence of prostate cancer in the world was thought to be among United States black men. The age adjusted rates in 1992 for United States black and white men were 249 and 182/100,000 respectively. The epidemiology of prostate cancer in Jamaica, a country of 2.5 million people of primarily African descent, was studied and compared with that of white and black Americans. MATERIALS AND METHODS: The study included 1,121 cases of prostate cancer diagnosed from 1989 to 1994. Sources of information included the Jamaican Cancer Registry, government pathology laboratory, hospital and clinic records, and physician office records. Incidence rates were computed using data from the 1991 Jamaican census. Age adjustments were made using the 1970 United States standard population. RESULTS: The average age adjusted incidence of prostate cancer in Kingston, Jamaica was 304/100,000 men. Median patient age at diagnosis was 72 years. More than 80 percent of the cases were pathologically confirmed. Of the patients 30 percent presented with acute urinary retention, 16 percent presented with bone metastases, 15 percent had gross hematuria at the time of diagnosis and an abnormal rectal examination suspicious for cancer was noted in 42 percent. Prostate specific antigen was measured in only 7 percent of cases in 1989 but in 48 percent of cases by 1994. CONCLUSIONS: These data demonstrate that Jamaican men in Kingston have a high incidence of prostate cancer, much higher than even black Americans during a similar period. Furthermore, the cancers are more significant clinically with greater morbidity in Jamaica than in the United States(AU)

Curso de reciclaje

El presente estudio desarrolla los métodos para organizar un proyecto de reutilización de desechos. Describe los sistemas de recolección ensayados y expresa cuáles resultan más recomendables; Aporta observaciones sobre los procesos de clasificación y almacenamiento de los reciclables obtenidos