Cardioprotective Effects of Curcumin-Nisin Based Poly Lactic Acid Nanoparticle on Myocardial Infarction in Guinea Pigs.

Myocardial infarction (MI) is the most prevalent cause of cardiovascular death. A possible way of preventing MI maybe by dietary supplements. The present study was thus designed to ascertain the cardio-protective effect of a formulated curcumin and nisin based poly lactic acid nanoparticle (CurNisNp) on isoproterenol (ISO) induced MI in guinea pigs. Animals were pretreated for 7 days as follows; Groups A and B animals were given 0.5 mL/kg of normal saline, group C metoprolol (2 mg/kg), groups D and E CurNisNp 10 and 21 mg/kg respectively (n = 5). MI was induced on the 7th day in groups B-E animals. On the 9th day electrocardiogram (ECG) was recorded, blood samples and tissue biopsies were collected for analyses. Toxicity studies on CurNisNp were carried out. MI induction caused atrial fibrillation which was prevented by pretreatment of metoprolol or CurNisNp. MI induction was also associated with increased expressions of cardiac troponin I (CTnI) and kidney injury molecule-1 (KIM-1) which were significantly reduced in guinea pig's pretreated with metoprolol or CurNisNp (P < 0.05). The LC50 of CurNisNp was 3258.2 µg/mL. This study demonstrated that the formulated curcumin-nisin based nanoparticle confers a significant level of cardio-protection in the guinea pig and is nontoxic.

Transgenic rescue implicates beta2-microglobulin as a diabetes susceptibility gene in nonobese diabetic (NOD) mice.

Type 1 diabetes in both humans and nonobese diabetic (NOD) mice results from T-cell-mediated autoimmune destruction of insulin-producing pancreatic beta cells. Linkage studies have shown that type 1 diabetes in NOD mice is a polygenic disease involving more than 15 chromosomal susceptibility regions. Despite extensive investigation, the identification of individual susceptibility genes either within or outside the major histocompatibility complex region has proven problematic because of the limitations of linkage analysis. In this paper, we provide evidence implicating a single diabetes susceptibility gene, which lies outside the major histocompatibility complex region. Using allelic reconstitution by transgenic rescue, we show that NOD mice expressing the beta(2) microglobulin (beta(2)M)(a) allele develop diabetes, whereas NOD mice expressing a murine beta(2)M(b) or human allele are protected. The murine beta(2)M(a) allele differs from the beta(2)M(b) allele only at a single amino acid. Mechanistic studies indicate that the absence of the NOD beta(2)M(a) isoform on nonhematopoietic cells inhibits the development or activation of diabetogenic T cells.

Clear cell sarcoma of soft parts. A case report and review of the literature.

The case of a 25-year-old woman with recurring and metastasizing clear cell sarcoma of soft parts (CCS) is presented. The clinical setting and pathological appearance were in agreement with the original cases described. This report serves to highlight the clinico-pathological features of this rare and aggressive malignancy with specific reference to prognostic markers and treatment.

Clear cell sarcoma of soft parts. A case report and review of the literature

The case of a 25-year-old woman with recurring and metastasizing clear cell sarcoma of soft parts (CCS) is presented. The clinical setting and pathological appearance were in agreement with the original cases described. This report serves to highlight the clinico-pathological features of this rare and aggressive malignancy with specific reference to prognostic markers and treatment.

The curvature and cholesterol content of phospholipid bilayers alter the transbilayer distribution of specific molecular species of phosphatidylethanolamine.

The curvature, cholesterol content, and transbilayer distribution of phospholipids significantly influence the functional properties of cellular membranes, yet little is known of how these parameters interact. In this study, the transbilayer distribution of phosphatidylethanolamine (PE) is determined in vesicles with large (98 nm) and small (19 nm) radii of curvature and with different proportions of PE, phosphatidylcholine, and cholesterol. It was found that the mean diameters of both types of vesicles were not influenced by their lipid composition, and that the amino-reactive compound 2,4,6-trinitrobenzenesulphonic acid (TNBS) was unable to cross the bilayer of either type of vesicle. When large vesicles were treated with TNBS, approximately 40% of the total membrane PE was derivatized; in the small vesicles 55% reacted. These values are interpreted as representing the percentage of total membrane PE residing in the outer leaflet of the vesicle bilayer. The large vesicles likely contained approximately 20% of the total membrane lipid as internal membranes. Therefore, in both types of vesicles, PE as a phospholipid class was randomly distributed between the inner and outer leaflets of the bilayer. The proportion of total PE residing in the outer leaflet was unaffected by changes in either the cholesterol or PE content of the vesicles. However, the transbilayer distributions of individual molecular species of PE were not random, and were significantly influenced by radius of curvature, membrane cholesterol content, or both. For example, palmitate- and docosahexaenoate-containing species of PE were preferentially located in the outer leaflet of the bilayer. Membrane cholesterol content affected the transbilayer distributions of stearate-, oleate-, and linoleate-containing species. The transbilayer distributions of palmitate-, docosahexaenoate-, and stearate-containing species were significantly influenced by membrane curvature, but only in the presence of high levels of cholesterol. Thus, differences in membrane curvature and cholesterol content alter the array of PE molecules present on the surfaces of phospholipid bilayers. In cells and organelles, these differences could have profound effects on a number of critical membrane functions and processes.

Docosahexaenoic acid (DHA) alters the phospholipid molecular species composition of membranous vesicles exfoliated from the surface of a murine leukemia cell line.

Previously, we presented evidence that the vesicles routinely exfoliated from the surface of T27A tumor cells arise from vesicle-forming regions of the plasma membrane and possess a set of lateral microdomains distinct from those of the plasma membrane as a whole. We also showed that docosahexaenoic acid (DHA, or 22:6n-3), a fatty acyl chain known to alter microdomain structure in model membranes, also alters the structure and composition of exfoliated vesicles, implying a DHA-induced change in microdomain structure on the cell surface. In this report we show that enrichment of the cells with DHA reverses some of the characteristic differences in composition between the parent plasma membrane and shed microdomain vesicles, but does not alter their phospholipid class composition. In untreated cells, DHA-containing species were found to be a much greater proportion of the total phosphatidylethanolamine (PE) pool than the total phosphatidylcholine (PC) pool in both the plasma membrane and the shed vesicles. After DHA treatment, the proportion of DHA-containing species in the PE and PC pools of the plasma membrane were elevated, and unlike in untreated cells, their proportions were equal in the two pools. In the vesicles shed from DHA-loaded cells, the proportion of DHA-containing species of PE was the same as in the plasma membrane. However, the proportion of DHA-containing species of PC in the vesicles (0.089) was much lower than that found in the plasma membrane (0.194), and was relatively devoid of species with 16-carbon acyl components. These data suggested that DHA-containing species of PC, particularly those having a 16-carbon chain in the sn-1 position, were preferentially retained in the plasma membrane. The data can be interpreted as indicating that DHA induces a restructuring of lateral microdomains on the surface of living cells similar to that predicted by its behavior in model membranes.

Docosahexaenoic acid (DHA) alters the structure and composition of membranous vesicles exfoliated from the surface of a murine leukemia cell line.

Membrane lipid microdomains are regions of the membrane thought to be functionally important, but which have remained poorly characterized because they have proven to be difficult to isolate. The exfoliation of small membranous vesicles from the cell surface is a continuous and normal activity in many cells. If microdomains are relatively large or stable, they may influence the structure and composition of exfoliated vesicles, which are easy to isolate. We tested the ability of docosahexaenoic acid (DHA), a fatty acid proposed to alter the structure of microdomains, to change the structure and composition of vesicles exfoliated from a murine leukemia cell line. Cells were cultured in normal and DHA-enriched media for 72 h, then washed and given a 15-h exfoliation period. Afterwards, the pooled vesicles and their parent plasma membrane were collected and analyzed. Vesicles and plasma membrane from cells grown in normal culture medium had similar fatty acid compositions, including equal, and low, proportions of DHA, but the vesicles had much more cholesterol and displayed higher anisotropy than the plasma membrane. When cells were grown in DHA-enriched medium, both the plasma membrane and exfoliated vesicles had 10-fold elevated levels of DHA in their phospholipids, with the DHA displacing other polyunsaturates. These cells released vesicles having significantly reduced levels of cholesterol and monoenoic fatty acids than those in normal culture. The anisotropy of these vesicles was also dramatically reduced. These data are consistent with DHA altering the structure and composition of membrane microdomains on the cell surface, and suggest that exfoliated vesicles may prove useful in the further study of membrane microdomains.

Culturally informed social work practice with American Indian clients: guidelines for non-Indian social workers.

Culturally informed social work health and mental health interventions directed toward American Indian clients must be harmonious with their environment and acculturation. This article discusses American Indian beliefs about health and illness and degrees of acculturation. Guidelines are offered to help non-Indian social workers design culturally appropriate interventions.

Women of courage: commercial sex workers mobilize for HIV / AIDS prevention in Nigeria.

PIP: The Calabar Project in Nigeria, which seeks to reduce the vulnerability of prostitutes to HIV infection, began informally in 1987. By 1988, a formal, community-based intervention was created to promote condom use, provide health education as well as literacy and vocational training, and seek better working and living conditions for the prostitutes. The first task of the Calabar Project was to overcome the resistance of the hotel owners and managers where the prostitutes work and to win the confidence of the women. The owners and managers had to be convinced that it was in their best interest for the women to insist on condom use by their clients. The women had to be informed about the nature of HIV/AIDS and to be convinced that the project sought improvements in their general welfare. This was accomplished by helping the prostitutes improve both their relationship with the local police and their access to health services. Negotiations with hotel owners stabilized the prostitutes' rent for a year to enable the women to increase their charges for services and reduce the number of clients they needed so they could insist on condom use. Peer educators were trained to provide health education and to teach prostitutes techniques to get clients to use condoms. Clients were reached through the prostitutes and by providing information to small groups in hotel bars. Condoms were initially distributed for free and eventually were sold through a social marketing program. Peer educators also encouraged prostitutes and their clients to use a clinic the project established to diagnose and treat sexually transmitted diseases. In 1993, the Calabar Project helped create a vocational and literacy training center to improve the women's ability to understand the complex issues related to HIV/AIDS and to give the women a way to supplement their income and improve their self-esteem. By this time, more than 60% of the women reported using condoms for all sex acts.^ieng

Membrane fluidity and hemilayer temperature sensitivity in trout hepatocytes during brief in vitro cold exposure.

Fluorescent membrane probes were used to assess the fluidity of hepatocyte plasma membranes (PM) from 20 degrees C-acclimated trout after exposure to 20 and 5 degrees C. PM isolated from cells after 6 h at 5 degrees C were significantly more fluid [fluorescence depolarization of 1,6-diphenyl-1,3,5-hexatriene (DPH)] than control membranes at both temperatures. The increased fluidity was sufficient to offset 45-50% of the cold-induced membrane ordering. In contrast, the fluidity of PM in intact cells from 20 degrees C-acclimated fish remained constant when exposed to 5 degrees C for a similar period. In addition, the fluidity of the inner hemilayer [1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene, p-toluenesulfonate (TMA-DPH)] was significantly less sensitive to temperature change than was the fluidity of the outer hemilayer [3-(p-(6-phenyl)-1,3,5-hexatrienyl)phenylpropionic acid (PA-DPH)]. Because the isolated membrane preparation was most likely enriched with canalicular membranes (based on 5'-nucleotidase recovery), these results suggest that the canalicular domain of the plasma membrane is preferentially modified during short-term cold exposure and that the fluidity of the inner hemilayer of the plasma membrane of intact cells is relatively temperature insensitive, thus requiring fewer modifications than the outer hemilayer during temperature acclimation.

Seroepidemiology of human immunodeficiency virus infection in Borno State of Nigeria by sentinel surveillance.

A serosurvey for human immunodeficiency virus (HIV) infection was carried out in three well-separated population centers in Borno State of Nigeria in 1989-1990. The study subjects were 1,259 made up of sexually transmitted disease (STD) clinic attenders, pregnant women, female prostitutes, and blood donors. Sera were screened by enzyme-linked immunosorbent assay and confirmation was done by Western blotting. The overall seroprevalence was 1.67% (21/1,259), with no significant differences from one population center to another. There were, however, significant differences among the population groups studied: prostitutes, 4.24%; STD clinic attenders, 1.67%; blood donors, 0.71%; and pregnant women, 0.24%. Of the 21 seropositives, 18 were positive for HIV-1 only; 1 was positive for HIV-2 only; and 2 were positive for both HIV-1 and HIV-2. All three HIV-2-positive sera were from prostitutes. Prevalence rates found in this study showed marked increases from 2 to 3 years earlier. There is therefore the need for a vigorous and sustained intervention program.

Psychological consequences of burn injury.

The major psychological sequelae experienced by patients 1 year after burn injury were investigated. Data were collected on a consecutive series of adult burn patients, (n = 55), including major demographic and epidemiological characteristics. Participants (n = 23) completed the Hospital Anxiety Depression Scale (HADS), the Impact of Event Scale (IES) and a questionnaire covering functional impairment, visibility of the burn, experience of pain, etc. Over one-third of the patients (36.4 per cent) were found to have premorbid characteristics which could predispose them to injury. Over one-third (34.7 per cent) were still experiencing significant psychological problems. Anxiety was most common, followed by posttraumatic stress symptoms and depression. The visibility of the burn was found to be a useful factor in the prediction of psychological outcome (P = 0.001-0.018). No additional variables were found to increase the significance of prediction. Patients indicated that practical advice in the form of staff-led discussions, before or immediately after discharge, would be the most valuable help.

Thermal adaptation in biological membranes: functional significance of changes in phospholipid molecular species composition.

Quantities of 1-palmitoyl 2-docosahexaenoyl phosphatidylcholine (16:0/22:6-PC or PDPC) increase from 24 to 40 weight percent as a consequence of cold acclimation in mitochondrial membranes of rainbow trout liver (J. Comp. Physiol. 156, 665-674, 1986). The present study was undertaken to assess the impact of such a large change in the proportions of a single molecular species on the fluidity, lateral packing (as sensed by phospholipase A2), and permeability of biological membranes. These properties were examined in multilamellar liposomes prepared from binary mixtures of dipalmitoyl phosphatidylcholine (DPPC) and PDPC in proportions increasing from 10 to 40 mole% PDPC. Glucose permeability was positively correlated with both assay temperature and PDPC content. The temperature dependence of Na+ permeability declined steadily as the mole fraction of PDPC increased; consequently, sodium permeability was positively correlated with PDPC content at 5 degrees C, but inversely correlated at 20 degrees C. Phospholipase A2 activity was independent of both assay temperature and vesicle composition. Vesicles of all compositions displayed a single transition in the temperature dependence of 1,6 diphenyl-1,3,5-hexatriene (DPH) fluorescence polarization, which shifted to lower temperature and broadened as proportions of PDPC increased. At temperatures below the transition, fluidity was positively correlated with the mole fraction of PDPC, but interfacial and deeper regions of the bilayer were affected differently by variations in PDPC content. Nonelectrolyte permeability was the only index of membrane structure or function to be significantly correlated with the fluidity of the bilayer interior. The tendencies of PDPC to both fluidize the membrane and to reduce the temperature sensitivity of electrolyte permeation may promote the adaptation of membrane function to low temperature.

The role of alterations in membrane lipid composition in enabling physiological adaptation of organisms to their physical environment.

It is clear from the literature reviewed that modifications in membrane lipid composition play a major role in the adaptation of diverse organisms to specific environments and physiological circumstances. Acyl chain and molecular species restructuring in phospholipids are the most ubiquitous adaptations to environmental insult, being implicated in membrane adjustments to temperature, pressure, water activity, pH and salinity. In contrast, other adaptations (e.g. modulation of anionic phospholipids (salinity adaptation), trehalose content (dehydration) and the PC/PE ratio (temperature acclimation] appear to be more context specific. Although the volume of correlative data relating membrane composition to environmental state is impressive, several questions must be explicitly addressed in future research if a mechanistic understanding of the role of lipids in fine tuning membrane function is to be achieved. These include: (1) Adaptation thresholds--How much environmental variation is required before an acclimatory response is initiated, and is the extent of membrane perturbation induced by such minimally effective stimuli similar for different stress vectors? Interspecific comparisons of the Na+/K(+)-ATPase of fish collected at different depths indicate that species must be separated in depth by a distance corresponding to a pressure difference of 20 MPa before pressure adaptation is evident. Assuming a dT/dP value of 0.23 (Table 1), a 20 MPa change in pressure corresponds to ca. a 5 degrees C change in temperature, which agrees well with the minimal temperature change required to elicit changes in the lipid composition of plasma membranes in kidney tissue of thermally-acclimating trout. A pressure of 20 MPa also corresponds approximately to the maximum depth from which deep sea animals survive being brought to the surface. Collectively, these observations suggest that the minimally effective stimuli for both temperature and pressure adaptation are similar. Comparable data are not available for other environmental variables. (2) Signal transduction--What signals are being sensed and how are they transduced into an adaptational response? In some cases, it is clear that the enzymes of lipid metabolism respond directly (either by a variation in catalytic rate or substrate preference) to variations in the physical environment in an apparently adaptive manner (e.g. refer Sections VI.A.1 and VI.B.2). It seems unlikely, however, that such direct effects can explain the totality of the adaptive capacity of organisms, especially given the evidence for the induction of desaturase synthesis in cold adaptation (refer to Section VI.A.2).(ABSTRACT TRUNCATED AT 400 WORDS)

Antibodies to human immunodeficiency virus (HTLV-III/LAV) in people from Lagos and Cross River States of Nigeria.

Using enzyme-linked immunosorbent assay (ELISA) and confirmatory immunoprecipitation tests, sera from 640 Nigerians from Lagos and Cross River States were examined for antibodies against HIV. These comprised 570 blood donors and their family members, 56 patients with various haematological conditions and 14 patients with acute Plasmodium falciparum infection. None of the sera was positive for HTLV-III/LAV antibodies by immunoprecipitation, although 12 (1.9%) sera were positive by ELISA.

Thermoregulatory behavior and temperature gradient perception in a juvenile fish (Poecilia reticulata).

The thermoregulatory behavior of guppies in a temperature gradient was studied under conditions offering one degree of locomotor freedom, in which displacement of the fish was coupled to a change of occupied temperature, and two degrees of locomotor freedom, in which the added dimension allowed for thermally neutral movement, thus uncoupling any obligatory link between displacement and temperature change. More animals failed to thermoregulate in the second than in the first geometrical system (32% vs. 7%); however, the means of the temperature preferenda (Tp) were the same in both gradient configurations and the frequency distributions along the temperature axis were indistinguishable. In both geometrical systems, mean swimming speed along the temperature axis showed well-defined minima coinciding with the Tp. It was shown that the mean components of movement with respect to the thermal and thermally neutral axes both showed minima at Tp. Further analyses of the actual behavior confirm that in the vicinity of Tp the movements of the fish show little dependence on direction. The analyses thus suggest that thermoregulatory movements are not adjusted in response to movement-generated directional information derived from the temperature gradient. The primary determinant of thermoregulatory behavior in fish may require a more complex awareness of the thermal arrangement of the environment than can be furnished by the instantaneous perception of the local gradient structure.