Glutamate-induced calcium signaling in astrocytes

Astrocytes respond to the excitatory neurotransmitter glutamate with dynamic spatio-temporal changes in intracellular calcium [Ca²⁺]_i. Although they share a common wave-like appearance, the different [Ca²⁺]_i changes--an initial spike, sustained elevation, oscillatory intracellular waves, and regenerative intercellular waves--are actually separate and distinct phenomena. These separate components of the astrocytic Ca²⁺ response appear to be generated by two different signal transduction pathways. The metabotropic response evokes an initial spatial Ca²⁺ spike that can propagate rapidly from cell to cell and appears to involve IP₃. The metabotropic response can also produce oscillatory intracellular waves of various amplitudes and frequencies that propagate within cells and are sustained only in the presence of external Ca²⁺. The ionotropic response, however, evokes a sustained elevation in [Ca²⁺]_i associated with receptor-mediated Na⁺ and Ca²⁺ influx, depolarization, and voltage-dependent Ca²⁺ influx. In addition, the ionotropic response can lead to regenerative intercellular waves that propagate smoothly and nondecrementally from cell to cell, possibly involving Na⁺/Ca²⁺ exchange. All these astrocytic [Ca²⁺]_i changes tend to appear wave-like, traveling from region to region as a transient rise in [Ca²⁺]_i. Nevertheless, as our understanding of the cellular events that underlie these [Ca²⁺]_i changes grows, it becomes increasingly clear that glutamate-induced Ca²⁺ signaling is a composite of separate and distinct phenomena, which may be distinguished not based on appearance alone, but rather on their underlying mechanisms. © 1994 Wiley-Liss, Inc.     

Should all the N3 lymph nodes group metastasis be regarded as distant metastasis (M1) in curatively resected gastric cancer?

Recently, metastasis to N3 lymph nodes group was regarded as distant metastasis by the new TNM staging system due to poor overall survival. However, the 5-year overall survival rate of patients with metastasis to N3 groups was 34.5% after curative surgery. Moreover, in patients with metastasis to lymph node subgroups of #12, #13, #14, the overall 5-year survival rate increased upto 47.2% after curative resection and adjuvant chemotherapy. This was similar to that of the patients with metastasis to N1 and N2 lymph nodes groups. But in these highly tumor burden states, no survival benefit was found with the addition of immunotherapy to chemotherapy as we achieved in stage II and III. Therefore, we suggest that, at least, metastasis to #12, #13, #14 lymph nodes subgroups should not be categorized as a distant metastasis. And in these situations, active curative radical surgery with extended lymphadenectomy and adjuvant chemotherapy are recommended.     

Update on the Interaction of Rifampin and Warfarin

A 79-year-old man with a history of deep vein thrombosis and pulmonary embolism received anticoagulation therapy with warfarin 5 mg daily for 8 months. He was diagnosed with osteomyelitis and underwent partial metatarsal resection of his right foot. After surgery, antibiotics were initiated including ertapenem sodium 1 g intravenously every 24 hours, vancomycin 1400 mg intravenously every 24 hours, and rifampin 300 mg by mouth twice daily. Achieving a therapeutic level of anticoagulation was difficult despite escalating doses of warfarin, because of the interaction with rifampin. A 5- to 6-fold increase in warfarin dose was prescribed to reach therapeutic international normalized ratios (INRs), but even these increases were insufficient to maintain his INR in the therapeutic range. After rifampin was discontinued, warfarin doses were gradually reduced over the next 2 months. When concurrent warfarin-rifampin therapy is necessary, vigilant monitoring is imperative and significant increases in warfarin doses are likely.     

Developing the future nurse leaders of Fiji.

BACKGROUND: Nurse leaders in Fiji are currently involved in meeting the challenges of being at the forefront of an AusAID supported Health Sector Improvement process. Fiji is experiencing the same shortages of health professionals (including nurses) as is occurring internationally, while simultaneously striving to improve the quality of its health services. PRIMARY ARGUMENT: This paper provides information about the current situation in relation to health services in Fiji, and describes strategies being undertaken by the nurse leaders of Fiji to meet the challenge of leading an exciting reform process. James Cook University, School of Nursing Sciences, has been privileged to support the provision of contemporary leadership and management education for current and future nurse leaders in the Fiji Health Sector as a component of a current education program to educate registered nurses to bachelor level. This paper will provide an overview of the current Fiji Health Sector Improvement Program, with a particular focus on the preparation of nurse leaders. CONCLUSION: There is an ongoing need to understand beliefs and values, and styles of interaction and communication, and indeed, ideas about time. With collaboration between Australian academics and Fiji tutors from the Fiji School of Nursing, the program appears to be remarkably successful.     

Transdermal permeation-enhancing activities of some inorganic anions

Effects of sodium salts of various monovalent inorganic anions on transdermal permeation of salicylic acid were investigated. In in-vitro experiment using a Franz-type diffusion cell and excised mouse skin, the permeation-enhancing activities of the sodium salts of inorganic anions were roughly proportional to lyotropic Hofmeister swelling abilities of the anions; F^?<SO₄ ^2?<Cl^? <ClO₄ ^?<NO₃ <SCN^? <Br <I^?, i.e. l, Br and SCN increased the flux of drugs through the mouse skin, while F^?, SO₄ ^2?, Cl^?, ClO₄ ^? and NO₃ ^? decreased or did not affect the flux. In invivo experiment using the rabbit as the test animal, the plasma concentration of salicylic acid of the rabbit to which 10%-salicylic acid ointment containing 5%-Nal or NaBr was applied was significantly higher than that of the rabbit to which the ointment without the electrolytes was applied. The amounts of sterol leached out of stratum corneum sheet when the sheet was immersed in aqueous solutions of Nal, NaBr, or NaSCN were much more than that of stratum corneum immersed in aqueous solutions of the other inorganic anions. The FTIR/ATR spectroscopy showed that the peaks at 2853 cm^?1 and 2924 cm^?1 in the IR absorption spectrum of the stratum corneum sheet of the mouse were shifted to higher frequencies by the anions which enhanced the transdermal drug permeation, while not shifted by the anions which did not have any permeation-enhancing activities or have permeation-reducing activities. These results suggest that sodium salts of some anions such as iodide, bromide and thiocyanate enhance transdermal permeation of salicylic acid through swelling and perturbation of the skin structure by these anions.     

Hwa-byung. A community study of Korean Americans.

One hundred nine Korean American community subjects were interviewed regarding their experiences with hwa-byung (HB), a Korean folk illness label commonly used by Koreans with a myriad of physiological and psychological complaints. During these interviews, standard instruments were also used to assess their depressive and somatic symptoms. The results indicated that a relatively high proportion (12%) of the subjects labeled themselves as having suffered from HB. While no apparent sociodemographic differences were found between HB and non-HB subjects, significantly more HB subjects fulfilled the diagnosis of DSM-III major depression and also had previous diagnoses of depression. The HB subjects also had significantly higher scores for the total, depressive, and somatic subscales and 16 of the 20 individual items of the Center for Epidemiologic Studies-Depression Scale. These data confirm previous observations of substantial overlap between HB and DSM-III major depression among Koreans and Korean Americans, and suggest that HB may be a culturally patterned way of expression for Koreans experiencing major depression and related conditions. The clinical and theoretical implications of these findings are also discussed.     

Femoral prosthesis implantation induces changes in bone stress that depend on the extent of porous coating

The objective of this study was to evaluate the effect of implantation of porous-coated anatomic medullary fitting prostheses on stress in the proximal femur. Three-dimensional finite element models of a cadaveric femur before and after implantation were used to evaluate the resulting changes in stress in the bone. Models of the femur were generated automatically from computed tomographic scan data with use of an innovative mesh-generation technique. The models were analyzed for three levels of porous coating (proximal, 5/8, and full), with the assumption of ideal ingrowth (perfect bonding) over porous areas and a frictionless, tension-free surface on smooth areas. All models were loaded and restrained to represent conditions of normal gait. The stresses predicted in the implanted femur are consistent with clinical observations of proximal cortical atrophy (normal stress reduced to 6-9% of normal at the calcar and 50–55% at mid-prosthesis) and of hypertrophy at the porous coating junctions (normal stress at the 5/8-coating junction, 123% of stress proximal to the junction) and hypertrophy near the distal tip of the prosthesis (anterior and posterior normal stresses 200–800% of normal). The fully coated prosthesis induced stresses in the bone near the tip of the prosthesis that were most like stresses in the normal femur (medial and lateral normal stress 105 and 102% of the stress in the normal femur). Below the collar, the normal stress associated with the proximally coated prosthesis was 6% greater than that produced with the other two levels of coating but still was only 2% of normal. The 5/8-coated prosthesis appeared to combine the worst features of the fully coated and proximally coated prostheses–greater stress-shielding at the calcar and higher stress near the tip of the prosthesis.     

Prognostic significance of echogenic lesion within small hepatocellular carcinoma]

To evaluate prognostic significance of echogenic lesion within small hepatocellular carcinoma (SHCC, less than or equal to 2 cm in diameter), clinical and pathological findings of 32 cases with SHCC containing echogenic lesion (echogenic SHCC) were compared with those of 55 cases with non-echogenic SHCC. Compared with the non-echogenic SHCC group, the frequency of clinical stage I was significantly higher, and there were significantly more cases with solitary tumor relative to cases with multiple tumors in the echogenic SHCC group. Histologically, the incidence of the HCC composed of well-differentiated tumor cells corresponding to Edmondson's grade I was significantly higher in the echogenic SHCC group than in the non-echogenic SHCC group. Although HCCs tended to become progressively less differentiated with increasing tumor sizes in the both groups, the process of cellular change appeared to proceed more slowly in the echogenic SHCC group. Survival rate after tumor detection was 73% at three years, 56% at five years and 48% at seven years and nine years in the echogenic SHCC group, while it was 46% at three years, 42% at five years and 0% at seven years in the non-echogenic SHCC group. The present results showed that the presence of echogenic lesion within SHCC could be useful prognostic indicator.