Future medicine for hypertension in the elderly

The number of the aged patients with hypertension is now explosively increasing. In near future, progress of new and tailor-made prescribed antihypertensive drugs and curable-gene therapy for hypertension will improve new era of hypertension in the elderly. And finally, resolusion of the aging mechanism and anti-aging medicine may open our future.     

Green tea polyphenol-induced epidermal keratinocyte differentiation is associated with coordinated expression of p57/KIP2 and caspase 14

Epigallocatechin-3-gallate (EGCG), the most abundant polyphenol in green tea, exerts chemopreventive effects by selectively inducing apoptosis in tumor cells. In contrast, EGCG accelerates terminal differentiation in normal human epidermal keratinocytes (NHEK) mediated partially by up-regulation of p57/KIP2, a cyclin-dependent kinase inhibitor that confers growth arrest and differentiation. However, it is unclear if EGCG modulates caspase 14, a unique regulator of epithelial cell terminal differentiation associated with cornification. Here, we examined the effect of EGCG on caspase 14 expression in NHEK and correlated the protein and mRNA expression of p57/KIP2 with those of caspase 14 in either normal keratinocytes or p57/KIP2-expressing tumor cells (OSC2, an oral squamous cell carcinoma cell line). Additionally, paraffin-embedded normal and untreated psoriatic (aberrant keratinization) skin sections from humans were assessed for caspase 14 by immunohistochemistry. In NHEK, EGCG induced the expression of caspase 14 mRNA and protein levels within a 24-h period. The expression of p57/KIP2 in OSC2 cells was adequate to induce caspase 14 in the absence of EGCG; this induction of caspase 14 was down-regulated by transforming growth factor-beta1. In human psoriatic skin samples, caspase 14 staining in the upper epidermis was reduced, especially in nuclear areas. These results suggest that, in addition to p57/KIP2, EGCG-induced terminal differentiation of epidermal keratinocytes involves up-regulation of caspase 14. Further understanding of how EGCG modulates cellular differentiation may be useful in developing green tea preparations for selected clinical applications.     

NMDA receptor-dependent oscillatory signal outputs from the retrosplenial cortex triggered by a non-NMDA receptor-dependent signal input from the visual cortex

The retrosplenial cortex is located at a critical juncture between the visual cortex and hippocampal formation. Functions of the retrosplenial cortex at the local circuit level, however, remain unclear. Herein, we show how signals traveling from the visual cortex behave in local circuits of the retrosplenial cortex, using optical recording methods and application of caffeine to rat brain slices. Electrical signals evoked in the primary visual cortex penetrated into the deep layer of the retrosplenial granular a cortex (RSGa) and propagated further toward postsubiculum and upper layer. Non-N-methyl-D-aspartate (NMDA) receptor-dependent initial traveling signal from the visual cortex triggered NMDA receptor-dependent neural oscillation in the RSGa. Oscillatory signals originated from the local area in the deep layer of the RSGa, and the signal spread back and forth toward the visual cortex and postsubiculum, in addition to spreading toward the upper layer. From the perspective of the RSGa, extrinsic signal inputs from the visual cortex switched on neural oscillators in the RSGa that deliver NMDA receptor-dependent intrinsic signal outputs. Opening and strengthening of non-NMDA receptor-dependent input pathways from the visual cortex required NMDA receptor-dependent oscillatory neural activities. These input and output relationships indicate that the retrosplenial cortex may represent an important relay station between the visual cortex and hippocampal formation.     

Computed tomography assessment of myocardial perfusion, viability, and function

In addition to coronary artery assessment, contrast-enhanced multidetector spiral computed tomography (CE-MDCT) can provide valuable information about myocardial perfusion. Using CE-MDCT, myocardial perfusion defects are often observed in the early phase of the contrast bolus (early defect (ED)), with residual defects (RDs) and late enhancement (LE) observed in the late phase in myocardial infarction (MI). However, the clinical significance of EDs, RDs, and LE has not yet been fully described. This work reviews myocardial viability and function by CE-MDCT based on our prior data by including contrast-enhanced single-slice (detector) CT (CE-SSCT) and CE-MDCT. Recently, equivalent results were obtained, as seen in CE-SSCT with images by CE-MDCT. In this review, images that were acquired by MDCT will be presented. In this work, the following items will be the focus: myocardial enhancement patterns (EDs, LE, and RDs), early perfusion defects and their relationship to wall thickness (WT) and wall motion, early CT perfusion defects vs. Tl-201 single photon emission CT (SPECT), the protocol for performing dual-phase contrast CT, classification of enhancement patterns, enhancement patterns on dual-phase CE-MDCT vs. left ventricular functional recovery and WT, changes in enhancement patterns in conjunction with healing stage, enhancement patterns on dual-phase CE-MDCT vs. 201Tl/99mTc-pyrophosphate (dual-isotope SPECT), the clinical meaning of each enhancement pattern, pitfalls of enhancement patterns and other diseases, and study limitations and the future of MDCT.     

Surgical Treatment of Bone Metastasis Followed by a Primary Lung Cancer Lesion: Report of a Case

In August 1997, a 68-year-old man presented with right pelvic pain. Pelvic computed tomography (CT) and bone scintigraphy showed a huge tumor of the right iliac bone. No other lesion was detected, in spite of a high serum carcinoembryonic antigen level (CEA, 963ng/ml). In October 1997, the iliac bone tumor was widely resected, and thereafter was diagnosed to be a metastatic adenocarcinoma of unknown origin. After a resection, the serum CEA level dropped as low as 6.4ng/ml, but gradually went up to 80ng/ml in October 1999. Next, a lung tumor in the left upper lobe was detected by routine chest CT. In January 2000, a left upper lobectomy was performed, and based on not only the pathological findings but also on an immunohistochemical analysis for napsin A expression, the tumor was diagnosed to be lung adenocarcinoma. The histological and immunohistochemical findings in the previously resected bone lesion were completely compatible with those in the pulmonary tumor, which was finally regarded as M1 lung cancer. In October 2002, the patient was alive without any symptoms, although the serum CEA level was elevated again. We consider this case worthy of presentation because of its unique clinical course as well as the successful long-term survival after surgical treatment alone, for both the primary and metastatic lesions.     

Intraoperative ultrasonography is useful for diagnosing pancreatic duct injury and adjacent tissue damage in a patient with penetrating pancreas trauma

We report a case of pancreatic injury, caused by a stab wound, in which ductal injury and wound depth were clearly identified by intraoperative ultrasonography. A 65-year-old woman was emergently admitted to our hospital after stabbing herself in the abdomen in a suicide attempt. Preoperative computed tomography (CT) and laboratory examination revealed liver and pancreatic injury with massive abdominal bleeding and free air. Operative findings included injuries of the stomach, small bowel, colon, liver, and pancreas. The pancreatic lacerations were 1cm in length, in the body. Intraoperative ultrasonography enabled the diagnosis of a lacerated main pancreatic duct with no damage to the major vessels posterior to the pancreas. Distal pancreatectomy; simple repairs of the liver, small bowel, and stomach; exteriorization of the injured colon; cholecystostomy; gastrostomy; and jejunostomy were performed. The patient recovered and was transferred to a psychiatric hospital 87 days after surgery. In this patient, intraoperative ultrasonography was successfully used to identify the degree of injury to the pancreatic duct, as well as the depth of the stab wound. In conclusion, intraoperative ultrasonography should be routinely performed to detect main pancreatic duct injury in penetrating pancreatic trauma.     

Induction of adipogenesis by the intrasplenic transplantation of chick serum clots

Chick serum contains a factor that stimulates adipogenesis in Meckel's chondrocytes in vitro. The present study examined whether chick serum has a capacity for adipogenic induction in vivo, by transplanting serum clots (created by drying chick serum for up to 4 weeks) into mouse spleens. Specimens were harvested for histological analyses, which included light and electron microscopy and immunohistochemistry. The transplanted serum clots induced the appearance of lipid droplet-containing cells in splenic cords and sinus. Almost all the lipid droplet-containing cells were positive for sudan staining and consisted of multilocular lipid vacuoles. Immunostaining showed that the adipocytes induced by transplantation of the serum clots initially appeared as peroxisome proliferator-activated receptor-gamma (PPARgamma)-positive cells and developed into leptin and alpha-glycerophosphate dehydrogenase (GPDH)-producing cells, in addition to type III collagen synthesis. Furthermore, double immunofluorescence staining revealed that the immunoreactivity for GPDH was detected not only in stromal cells but also in macrophages. It was thus confirmed that stromal cells and macrophages in the spleen contain lipid droplets as seen in intact white adipose cells. The present results suggest that chick serum contains factors for adipocyte induction not only in vitro but also in vivo, and that the adipogenic potential does not depend on the supplements used during the cell culture.