AbstractHyperglycemia increases cerebral damage after transient cerebral ischemia. This study used in vivo 31P nuclear magnetic resonance spectroscopy to determine the relationship of intracellular tissue acidosis and delayed recovery of brain high-energy phosphates to increased damage during the reperfusion period. Mongolian gerbils were subjected to transient bilateral carotid ischemia for 20 min with 2 h reperfusion. All gerbils were pretreated intraperitoneally with equivalent volumes in saline of 0.003 units per kilogram of insulin or vehicle, or with 4 grams of glucose per kilogram. The gerbils were then scanned in a 4.7 Tesla Magnetic Resonance Imager-Spectrometer to determine levels of intracellular pH, inorganic phosphate, adenosine triphosphate, and phosphocreatine. In each group, intracellular pH decreased with ischemia, but most significantly in hyperglycemic animals (6.45±0.15), in which it had not recovered to pre- ischemic levels by the end of the reperfusion period (6.8 ±0.1 vs 7.04 ±0.1, p <0.05). High-energy phosphates phosphocreatine-inorganic phosphate and phosphocreatine-adenosine triphosphate showed partial recovery in all groups throughout the reperfusion period; the recovery was not significantly altered by glucose status. Hyperglycemia worsened pH but not the recovery of high-energy phosphates in animals reperfused after 20 min of transient cerebral ischemia. This sustained acidosis may be a primary event in transient damage in hyperglycemic animals. [Neurol Res 1996; 18: 546-552] 相似文献
To investigate the ability of the fatigue, resistance, ambulation, incontinence or illness, loss of weight, nutritional approach, and help with dressing (FRAIL-NH) tool to predict mortality.
Design
The Incidence of Pneumonia and Related Consequences in Nursing Home Residents (INCUR) study database was used. This was an observational cohort study in French nursing homes conducted over 12 months in 2012.
Participants
A total of 788 residents aged 60 years or older, from 13 randomly selected French nursing homes.
Measurements
FRAIL-NH was generated from the available variables at baseline. FRAIL-NH scores ranged from 0 to 14 and people were categorized as nonfrail (0?1), frail (2?5), and most frail (6?14). Mortality data were obtained from medical charts and confirmed by the nursing home administrative documentation.
Results
Mean age of the participants was 86.2 ± 7.5 years, and 74.5% were women. The prevalence of persons with FRAIL-NH score greater than 1 was 88.8%, with 54.2% and 34.6% of residents identified as most frail and frail, respectively. The mean FRAIL-NH score was 6.0 ± 3.4. Women (N = 583) were frailer (6.1 ± 3.4) than men (N = 200, 5.5 ± 3.4; P = .027). Overall, 136 residents died over the 1-year follow-up period. The FRAIL-NH score was a predictor of mortality (adjusted hazard ratios: for frail group 1.15, 95% confidence interval 0.55?2.41; for most frail group 2.14, 95% confidence interval 1.07? 4.27).
Conclusions
FRAIL-NH is a predictor of mortality in nursing home residents and the score could assist with guiding appropriate care planning. 相似文献
Introduction: The major challenge of first pass metabolism in oral drug delivery can be surmounted by directing delivery toward intestinal lymphatic system (ILS). ILS circumvents the liver and transports drug directly into systemic circulation via thoracic duct. Lipid and polymeric nanoparticles are transported into ILS through lacteal and Peyer’s patches. Moreover, surface modification of nanoparticles with ligand which is specific for Peyer’s patches enhances the uptake of drugs into ILS. Bioavailability enhancement by lymphatic uptake is an advantageous approach adopted by scientists today. Therefore, it is important to understand clear insight of ILS in targeted drug delivery and challenges involved in it.
Areas covered: Current review includes an overview of ILS, factors governing lymphatic transport of nanoparticles and absorption mechanism of lipid and polymeric nanoparticles into ILS. Various ligands used to target Peyer’s patch and their conjugation strategies to nanoparticles are explained in detail. In vitro and in vivo models used to assess intestinal lymphatic transport of molecules are discussed further.
Expert opinion: Although ILS offers a versatile pathway for nanotechnology based targeted drug delivery, extensive investigations on validation of the lymphatic transport models and on the strategies for gastric protection of targeted nanocarriers have to be perceived in for excellent performance of ILS in oral drug delivery. 相似文献
Leber congenital amaurosis (LCA4) has been linked to mutations in the photoreceptor-specific gene Aryl hydrocarbon interacting protein like 1 (Aipl1). To investigate the essential role of AIPL1 in retina, we generated a mouse model of LCA by inactivating the Aipl1 gene. In Aipl1–/– retinas, the outer nuclear layer develops normally, but rods and cones then quickly degenerate. Aipl1–/– mice have highly disorganized, short, fragmented photoreceptor outer segments and lack both rod and cone electroretinogram responses. Recent biochemical evidence indicates that AIPL1 can enhance protein farnesylation. Our study reveals that rod cGMP phosphodiesterase, a farnesylated protein, is absent and cGMP levels are elevated in AIPL1–/– retinas before the onset of degeneration. Our findings demonstrate that AIPL1 enhances the stability of phosphodiesterase and is essential for photoreceptor viability. 相似文献
Patients with hepatitis B e antigen (HBeAg)‐positive chronic hepatitis B (CHB) have suppressed TLR2 expression, function and cytokine production. The aim of this study was to explore the importance of hepatitis B virus (HBV) genotype in innate immune responses and investigate whether Toll‐like receptor (TLR) expression/function has potential roles as predictive biomarkers of successful therapy with pegylated interferon (Peg‐IFN) therapy of HBeAg seroconversion in HBeAg‐positive patients. We showed that as early as 4 weeks after initiation of Peg‐IFN, future HBeAg seroconverters had significantly elevated levels of TLR2 expression on monocytes. TLR2‐associated IL‐6 production at baseline and week 4 of therapy and TLR4 IL‐6 production at week 4 were also markedly elevated in HBeAg seroconverters. HBV genotype also influenced treatment response, with genotypes A and B more likely to seroconvert than D. We were able to demonstrate that these differences were due in part to the interaction of the specific HBeAg proteins with TLR pathway adaptor molecules, and these interactions were genotype dependent. HBeAg‐mediated modulation of TLR signalling was also observed in Huh7 cells, following stimulation with Pam3Cys. Importantly, the addition of IFN‐α to TLR2‐stimulated cells cotransfected with an HBeAg expression plasmid reversed HBeAg‐mediated suppression of hepatocytes. These findings demonstrate that patients with an activated inflammatory response are much more likely to respond to IFN therapy, with TLR responses showing promise as potential biomarkers of HBeAg seroconversion in this setting. Furthermore, our findings suggest there is differential genotype‐specific HBeAg suppression of innate signalling pathways which may account for some of the clinical differences observed across the CHB spectrum. 相似文献
The goal of ovarian cancer screening is to detect disease when confined to the ovary (stage I) and thereby prolong survival. We believe this is an elusive goal because most ovarian cancer, at its earliest recognizable stage, is probably not confined to the ovary. We propose a new model of ovarian carcinogenesis based on clinical, pathological, and molecular genetic studies that may enable more targeted screening and therapeutic intervention to be developed. The model divides ovarian cancer into 2 groups designated type I and type II. Type I tumors are slow growing, generally confined to the ovary at diagnosis and develop from well-established precursor lesions so-called borderline tumors. Type I tumors include low-grade micropapillary serous carcinoma, mucinous, endometrioid, and clear cell carcinomas. They are genetically stable and are characterized by mutations in a number of different genes including KRAS, BRAF, PTEN, and beta-catenin. Type II tumors are rapidly growing, highly aggressive neoplasms that lack well-defined precursor lesions; most are advanced stage at, or soon after, their inception. These include high-grade serous carcinoma, malignant mixed mesodermal tumors (carcinosarcomas), and undifferentiated carcinomas. The type II tumors are characterized by mutation of TP53 and a high level of genetic instability. Screening tests that focus on stage I disease may detect low-grade type I neoplasms but miss the more aggressive type II tumors, which account for most ovarian cancers. A more rational approach to early detection of ovarian cancer should focus on low volume rather than low stage of disease. 相似文献
Scrub typhus has struck back, albeit with renewed vigour, impacting areas with previously known endemicity as also impressing newer expanses. It is not surprising, therefore, that Scrub typhus has emerged as a leading cause of public health concern globally as well as in India, but are we ready to take on the challenge?Over the last decade, there has been a global increase in the number of outbreaks of Scrub typhus, be it the military occupied areas or the civil population at large. The innumerable outbreaks of Scrub typhus, although disconcerting, have nonetheless contributed phenomenally towards better understanding of the dynamics of scrub typhus. There have been significant contributions to awareness of the disease amongst medical professionals, scrub typhus as a cause of Acute Undifferentiated Febrile Illness (AUFI) and newer clinical manifestation – Acute Encephalitis Syndrome (AES), availability and advances in diagnostics and management, man-vector-pathogen interactions, new records of Leptotrombidium species, newer vectors and Orientia species.Antigenic diversity and the varied clinical presentation of scrub typhus, absence of scrub typhus surveillance system and a lack of political will to recognize the disease as one of the important reemerging public health problem are areas seeking concerted deliberations and actions so that the challenges posed by scrub typhus can be addressed. 相似文献