Moderate-intensity continuous training reduces triglyceridemia and improves oxygen consumption in dyslipidemic apoCIII transgenic mice.

This study aimed to investigate metabolism modulation and dyslipidemia in genetic dyslipidemic mice through physical exercise. Thirty-four male C57Bl/6 mice aged 15 months were divided into non-transgenic (NTG) and transgenic overexpressing apoCIII (CIII) groups. After treadmill adaptation, the trained groups (NTG Ex and CIII Ex) underwent an effort test to determine running performance and assess oxygen consumption (V̇O2), before and after the training protocol. The exercised groups went through an 8-week moderate-intensity continuous training (MICT) program, consisting of 40 min of treadmill running at 60% of the peak velocity achieved in the test, three times per week. At the end of the training, animals were euthanized, and tissue samples were collected for ex vivo analysis. ApoCIII overexpression led to hypertriglyceridemia (P<0.0001) and higher concentrations of total plasma cholesterol (P<0.05), low-density lipoprotein (LDL) cholesterol (P<0.01), and very low-density lipoprotein (VLDL) cholesterol (P<0.0001) in the animals. Furthermore, the transgenic mice exhibited increased adipose mass (P<0.05) and higher V̇O2peak compared to their NTG controls (P<0.0001). Following the exercise protocol, MICT decreased triglyceridemia and cholesterol levels in dyslipidemic animals (P<0.05), and reduced adipocyte size (P<0.05), increased muscular glycogen (P<0.001), and improved V̇O2 in all trained animals (P<0.0001). These findings contribute to our understanding of the effects of moderate and continuous exercise training, a feasible non-pharmacological intervention, on the metabolic profile of genetically dyslipidemic subjects.

Analysis of natural resistance-associated macrophage protein-1 (NRAMP-1) level based on death, comorbidities and severity of COVID-19 patients: a cross-sectional study.

An accurate diagnosis of COVID-19 is essential for pandemic control and for establishing adequate therapeutic strategies to reduce morbidity and mortality. COVID-19 infection replicates in macrophage cells and affects the immune system. Natural resistance-associated macrophage protein-1 (NRAMP-1) carries cation ions, such as Fe2+, Zn2+ and Mn2+, and plays an essential role in the immune system to infection with micro-organisms. In addition, the function of NRAMP-1 is to limit the replication of pathogens by changing the phagosomal environment. Levels of NRAMP-1 protein are based on death, comorbidities and clinical symptoms of COVID-19 patients and it is possible for the soluble protein NRAMP-1 level to be used as an additional biomarker for forensic and medicolegal related COVID-19 cases and prosecutions from patients and families. Methods: Determination of NRAMP-1 protein levels using the enzyme link-immunosorbent assay technique in death, had comorbidities and severity of clinical symptoms of COVID-19 patients. Results: Of the 62 patients who received treatment, 10 patients died with an average NRAMP-1 level of 650 ng/ml and 52 patients who survive with an average NRAMP-1 level of 1065.26 ng/ml. The results of the study also found that 34 patients had comorbidities with an average NRAMP-1 level of 838.82 ng/ml and 28 patients without comorbidities with an average NRAMP-1 level of 1191.92 ng/ml. Based on the severity of clinical symptoms in survive patients, 10 patients with mild were found with an average NRAMP-1 level of 984.31 ng/ml, with moderate in 31 patients with an average NRAMP-1 level of 1104.71 ng/ml and severe in 11 patients with an average NRAMP-1 level of 1027.71 ng/ml. Conclusions: NRAMP-1 protein levels were significantly lower in COVID-19 patients who died and had comorbidities.

CD8+ TILS Expression in Invasive Breast Carcinoma (No Special Type).

Invasive breast carcinoma (IBC) is the most cancer in women (24%) and the cause of cancer death in women worldwide. Based on data from globocan 2018 shows the incidence of breast cancer is around 2.08 million (11.6%) which is the second rank of all cancers after lung cancer with a mortality rate of 626.6 thousand (6.6%) which is also the most common cause of death in women. The basic role of the immune system in maintaining homeostasis by immunosurveillance and initiation of the inflammatory reactions that include coordination of innate and adaptive immune cells activation against tumor cells is one of the most important in the mechanism of tumor cell elimination. Prognosis of IBC were influenced by several factors, including tumor histology grade and Tumor Infiltrating Lymphocytes (TILs). Infiltration of lymphocytes in the tumor microenvironment/TILs through CD8+ T lymphocytes is known to be an important component of adaptive immunity that eliminates tumor cells. CD8+ T cells present tumor antigens on the surface of the major histocompatibility complex class I (MHC class I). Based on its importance in clinical application and it's role in biological concepts, this study was conducted to determine the expression of CD8+ in Invasive Breast Carcinoma of No Special Type (IBC-NST) grades 1,2 and 3. Analytical study with a cross-sectional design on IBC-NST samples from 2017 until 2020 at the Laboratory of Anatomic Pathology, Faculty of Medicine, Hasanuddin University Makassar from May to August 2021. Immunoexpression data were analyzed to determine its relationship with grade. Eighty samples met the inclusion and exclusion criteria, there were 17 samples (21.3%) with grade 1, 32 samples (40%) with grade 2, and 31 samples (38.8%) with grade 3. In the high CD8+ TILs group, from a total of 27 samples, 10 samples with grade 1, 6 samples with grade 2, and as many as 11 samples with grade 3. In the low CD8+ TILs group, from a total of 53 samples, there were 7 samples with grade 1, 26 samples with grade 2, and 20 samples with grade 3. Based on the Chi-square test, p value = 0.017 (p <0.05). There is a significant difference in CD8+ TILS in Invasive Breast Carcinoma of No Special Type grade 1, grade 2 and grade 3.

Association of chemokine (CXC motif) receptor 4 expression with lymphovascular invasion and lymph node metastasis of invasive breast cancer.

BACKGROUND: The histological tumor grade influences the prognosis of breast cancer. In metastatic breast cancer, stromal cells produce chemokine (CXC motif) ligand 12 or stromal cell-derived factor-1 as a chemoattractant, which binds to chemokine (CXC motif) receptor 4 (CXCR4) expressed by breast cancer cells. OBJECTIVE: This study aimed to determine the expression of CXCR4 in invasive breast cancer in relation to lymphovascular invasion (LVI) and lymph node metastasis. METHODS: This observational study retrospectively investigated a paraffin block archived sample diagnosed with invasive breast cancer. The results of immunohistochemical staining with CXCR4 antibody and expression analysis were evaluated using light microscopy. The data were statistically analyzed using the chi-square test and presented in a table using SPSS version 18. P-values of <0.05 were considered statistically significant. RESULTS: The expression of CXCR4 was significantly associated with the incidence of LVI and lymph node metastasis in invasive breast cancer (both p = 0.001). CONCLUSIONS: The results show that the expression of CXCR4 varies and support its decisive role in the incidence of LVI and lymph node metastasis in invasive breast cancer.

CD133 Act as an Essential Marker in Ovarian Carcinogenesis.

OBJECTIVE: To analyze the role of cancer stem cells (CSC) in ovarian carcinogenesis through the identification of CD133 expression in the normal ovary (NO), serous cystadenoma (SC), borderline serous tumour (BST), low-grade serous carcinoma (LGSC), and high-grade serous carcinoma (HGSC). MATERIALS AND METHODS: A total of 48 tissue samples contain 5 NO, 10 SC, 5 BST, 8 LGSC, and 20 HGSC were stained with anti-CD133 antibody by immunohistochemical protocol. The difference in the H-score of CD133 expression between groups and their relationship to age, histomorphology, and localization was analyzed. RESULTS: CD133 expression varied among tumor groups, with clinicopathologic parameters showing diverse associations (age p = 0.773; histomorphology p = 0.001; and localization p = 0.026). The comparison of CD133 H-scores differed significantly between each group (p = 0.0031), in which precursor and malignant lesions possessed more robust CD133 expression. CONCLUSION: The presence of CD133 cellular expression and localization in different types of serous ovarian tumours suggests that these markers are involved in ovarian tumorigenesis.

Gata-3 and KI-67 expression in correlation with molecular subtypes of breast cancer.

OBJECTIVES: This study aims to evaluate and compare four breast cancer subtypes defined by immunohistochemistry expression of ER, PR, and HER-2 in correlation with Ki-67 and GATA-3 expression. METHODS: Slides from 89 paraffin blocks of invasive breast cancer patients with four molecular subtypes based on HER-2, ER, and PR expression were then stained with Ki-67 and GATA-3 antibodies to evaluate their expression in correlation with molecular subtype and metastases to lymph nodes. RESULTS: This study was a retrospective study of 89 invasive breast cancers. Luminal A; Luminal B; HER2+; and triple-negative types were 35 (39.3%), 10 (11.2%), 27 (30.3%), and 17 (19.1%) samples. Expression of Ki-67 was increased in triple-negative (TN) tumor compared to non-triple-negative (non-TN) tumor subtypes (p < 0.05). This Ki-67 expression was inversely correlated with the positivity of hormone receptor expression related to lymph-node metastases in TN-type tumors. Sixty-two (57%) samples were immunohistochemically positive for GATA-3. GATA-3 positive samples were significantly more likely to be ER and PR-positive, Ki-67 negative, and luminal A tumors. CONCLUSIONS: Subtype triple-negative breast cancer correlates with high expression of Ki-67 that contributes to poor prognosis of this subtype. The higher Ki-67 expression was correlated with the absence of hormone receptor expression compared with the negativity of Her-2 expression, downplay a role in nodal metastases in a triple-negative tumor. GATA-3 positive breast cancer showed luminal differentiation characterized by high ER expression and mainly was classified as luminal A type tumor with a better prognosis.

Programmed death-ligand 1 expression and tumor-infiltrating lymphocytes in colorectal adenocarcinoma.

BACKGROUND: Programmed death-ligand 1 (PD-L1) expression and tumor-infiltrating lymphocytes (TILs) are considered have a prognostic value in several malignancies. This study investigated the correlation between PD-L1 expression of tumor cells with the degree of stromal TILs in colorectal adenocarcinoma. METHODS: A cross sectional study design performed by taking 52 colorectal adenocarcinoma samples. The specimens were stained by immunohistochemical procedure using PD-L1 rabbit monoclonal antibody and the degrees of TILs were assessed base on hematoxylin and eosin (H&E) staining. RESULTS: From a total of 52 samples, the positive PD-L1 expression of tumor cells were 44 (84.6%) samples with 22 (50.0%), 18 (40.9%) and 4 (9.1%) samples had low-, moderate-, and high-degree TILs, respectively. While the negative PD-L1 expression were eight (15.4%) samples with 1 (12.5%), three (37.5%) and four (50.0%) samples had low-, moderate-, and high-degree TILs, respectively. A value of P=0.017 (P<0.05) was obtained by the Chi-square test. CONCLUSIONS: This study concluded that there was a significant correlation between PD-L1 expression of tumor cells and the degree of TILs in colorectal adenocarcinoma. This result indicated that the degree of TILs had the potential to be used as a predictive factor for PD-L1 expression of tumor cells in colorectal adenocarcinoma.

Moderate-intensity continuous training reduces triglyceridemia and improves oxygen consumption in dyslipidemic apoCIII transgenic mice

This study aimed to investigate metabolism modulation and dyslipidemia in genetic dyslipidemic mice through physical exercise. Thirty-four male C57Bl/6 mice aged 15 months were divided into non-transgenic (NTG) and transgenic overexpressing apoCIII (CIII) groups. After treadmill adaptation, the trained groups (NTG Ex and CIII Ex) underwent an effort test to determine running performance and assess oxygen consumption (V̇O2), before and after the training protocol. The exercised groups went through an 8-week moderate-intensity continuous training (MICT) program, consisting of 40 min of treadmill running at 60% of the peak velocity achieved in the test, three times per week. At the end of the training, animals were euthanized, and tissue samples were collected for ex vivo analysis. ApoCIII overexpression led to hypertriglyceridemia (P<0.0001) and higher concentrations of total plasma cholesterol (P<0.05), low-density lipoprotein (LDL) cholesterol (P<0.01), and very low-density lipoprotein (VLDL) cholesterol (P<0.0001) in the animals. Furthermore, the transgenic mice exhibited increased adipose mass (P<0.05) and higher V̇O2peak compared to their NTG controls (P<0.0001). Following the exercise protocol, MICT decreased triglyceridemia and cholesterol levels in dyslipidemic animals (P<0.05), and reduced adipocyte size (P<0.05), increased muscular glycogen (P<0.001), and improved V̇O2 in all trained animals (P<0.0001). These findings contribute to our understanding of the effects of moderate and continuous exercise training, a feasible non-pharmacological intervention, on the metabolic profile of genetically dyslipidemic subjects.

Blood amino acids concentration during insulin induced hypoglycemia in rats: the role of alanine and glutamine in glucose recovery.

Our purpose was to determine the blood amino acid concentration during insulin induced hypoglycemia (IIH) and examine if the administration of alanine or glutamine could help glycemia recovery in fasted rats. IIH was obtained by an intraperitoneal injection of regular insulin (1.0 U/kg). The blood levels of the majority of amino acids, including alanine and glutamine were decreased (P < 0.05) during IIH and this change correlates well with the duration than the intensity of hypoglycemia. On the other hand, the oral and intraperitoneal administration of alanine (100 mg/kg) or glutamine (100 mg/kg) accelerates glucose recovery. This effect was partly at least consequence of the increased capacity of the livers from IIH group to produce glucose from alanine and glutamine. It was concluded that the blood amino acids availability during IIH, particularly alanine and glutamine, play a pivotal role in recovery from hypoglycemia.

Exercise partially reverses the inhibitory effect of caffeine on liver gluconeogenesis in type 1 diabetic rats with hypoglycemia.

The purpose was to determine the possible effects of exercise and/or caffeine on hypoglycemia and liver gluconeogenesis in diabetic rats. These were divided into four subgroups: (a) intraperitoneal insulin only, (b) exercise bout before insulin, (c) caffeine after insulin, and (d) exercise bout before and caffeine after insulin. The marked glycemic drop 45 min after insulin (0 min = 229.00, 45 min = 75.75) was considerably reduced (p < 0.05) by caffeine or exercise (45 min: exercise = 127.00, caffeine = 104.78). However, this systemic effect was lost (p > 0.05) when they were combined (45 min: exercise + caffeine = 65.44) (Mean, in mg·dL-1). Caffeine alone strongly inhibited liver glucose production from 2 mM lactate 45 min after insulin (without caffeine = 3.05, with caffeine = 0.27; p < 0.05), while exercise + caffeine partially re-established the liver gluconeogenic capacity (exercise + caffeine = 1.61; p < 0.05 relative to the other groups) (Mean, in µmol·g-1). The improved hypoglycemia with caffeine or exercise cannot be explained by their actions on liver gluconeogenesis. As their beneficial effect disappeared when they were combined, such association in diabetic patients should be avoided during the period of hyperinsulinemia due to the risk of severe hypoglycemia.

Atherosclerosis in aged mice over-expressing the reverse cholesterol transport genes.

We determined whether over-expression of one of the three genes involved in reverse cholesterol transport, apolipoprotein (apo) AI, lecithin-cholesterol acyl transferase (LCAT) and cholesteryl ester transfer protein (CETP), or of their combinations influenced the development of diet-induced atherosclerosis. Eight genotypic groups of mice were studied (AI, LCAT, CETP, LCAT/AI, CETP/AI, LCAT/CETP, LCAT/AI/CETP, and non-transgenic) after four months on an atherogenic diet. The extent of atherosclerosis was assessed by morphometric analysis of lipid-stained areas in the aortic roots. The relative influence (R2) of genotype, sex, total cholesterol, and its main sub-fraction levels on atherosclerotic lesion size was determined by multiple linear regression analysis. Whereas apo AI (R2 = 0.22, P < 0.001) and CETP (R2 = 0.13, P < 0.01) expression reduced lesion size, the LCAT (R2 = 0.16, P < 0.005) and LCAT/AI (R2 = 0.13, P < 0.003) genotypes had the opposite effect. Logistic regression analysis revealed that the risk of developing atherosclerotic lesions greater than the 50th percentile was 4.3-fold lower for the apo AI transgenic mice than for non-transgenic mice, and was 3.0-fold lower for male than for female mice. These results show that apo AI overexpression decreased the risk of developing large atherosclerotic lesions but was not sufficient to reduce the atherogenic effect of LCAT when both transgenes were co-expressed. On the other hand, CETP expression was sufficient to eliminate the deleterious effect of LCAT and LCAT/AI overexpression. Therefore, increasing each step of the reverse cholesterol transport per se does not necessarily imply protection against atherosclerosis while CETP expression can change specific atherogenic scenarios.

Transcutaneous drug delivery: a practical review.

OBJECTIVE: To describe the advantages, disadvantages, practical considerations, and future developments of transcutaneous drug delivery. MATERIALS AND METHODS: The physiochemical properties of the drug preparation that are factors in the effectiveness of transcutaneous transport are drug stability or volatility, use of a solvent carrier or vehicle, use of a penetration enhancer, and type of delivery device. Because a drug should remain on the skin without evaporating or becoming otherwise inactive, it is suspended in a vehicle--any gel, lotion, or paste used to apply the drug to the skin. Penetration enhancers include several compounds that are mixed into vehicles to alter the molecular environment of the epidermis and facilitate absorption. The delivery system itself occasionally proves to be the ultimate determinant of transdermal drug flow. RESULTS: The advantages of transcutaneous drug delivery are avoidance of the gastrointestinal tract and hepatic first-pass biotransformation and metabolism, control of absorption, availability of multiple skin sites to avoid local irritation and toxicity, and improved patient compliance. The disadvantages include the potential for localized irritant and allergic cutaneous reactions, systemic toxicity, and difficulties associated with the time necessary for a drug to diffuse through the skin. CONCLUSION: Transdermal drug regimens are safe and effective. They provide clinicians the opportunity to offer more therapeutic options to their patients to optimize their care.

Thyroid hormone increases plasma cholesteryl ester transfer protein activity and plasma high-density lipoprotein removal rate in transgenic mice.

Thyroid dysfunction produces multiple alterations in plasma lipoprotein levels, including high-density lipoprotein (HDL). Cholesteryl ester transfer protein (CETP) and hepatic lipase (HL) are important proteins that modulate the metabolism of HDL. Thus, the effect of thyroid hormone on the activities of CETP and of HL was investigated using hypothyroid and hyperthyroid CETP transgenic (Tg) and nontransgenic (nTg) mice. Hyperthyroid Tg mice plasma lipoprotein (LP) profile analysis showed a significant increase in the very-low-density lipoprotein (VLDL) fraction (P <.001) and decrease in the HDL fraction (P <.005), whereas in the hypothyroid Tg mice an increase in low-density lipoprotein (LDL) was observed (P <.02). CETP activity was measured as the transfer of (14)C-cholesteryl ester (CE) from labeled HDL to LDL by an isotopic assay indicative of mass. Hyperthyroid Tg mice had twice as much plasma CETP activity as compared with their controls, while in hypothyroid Tg mice plasma CETP activity did not change. The role of CETP in determining the changes in LP profile of hyperthyroid animals was confirmed by showing that nTg wild-type hyperthyroid and euthyroid mice exhibited the same percent cholesterol distribution in LP. Postheparin HL activity measured in hyperthyroid Tg mice was significantly reduced (P <.05). (3)H-cholesteryl oleoyl ether ((3)H-Cet)-HDL plasma fractional removal rate (FRR) was approximately 2-fold faster in the hyperthyroid Tg mice than in controls, but was not modified in hypothyroid animals. Tissue uptake of (3)H-Cet was examined in 10 tissue samples: levels were significantly increased in skeletal muscle and decreased in small intestine in hyperthyroid Tg mice, and decreased in the small intestine of hypothyroid Tg mice. In conclusion, the excess of thyroid hormone accelerates HDL metabolism in CETP transgenic mice mainly due to an increase in plasma CETP activity and independently from the HL activity. Hypothyroid status did not change CETP activity and HDL metabolism.

Temporal and spatial patterns of malaria reinfection in northeastern Venezuela.

We stratified the risk of malaria transmission (Plasmodium vivax) in 35 villages along a coastal range in northeastern Venezuela (51 km2) where the main vector is the mosquito Anopheles aquasalis. After 20 years without local malaria transmission, reinfection of the entire area occurred from May to December 1985 by local (continuous) and jump (discontinuous) dispersal. Epidemiologic, environmental, and vector variables were investigated with the aid of a Geographic Information System. Risk factors for malaria transmission were human population density, proximity to pre-adult mosquito habitats (< 500 m), and the number of pre-adult habitats nearby. Most inhabitants, immature mosquito habitats, and malaria cases were located at low elevations and on gentle slopes. High prevalence of malaria during the dry seasons was associated with the presence of permanent bodies of water containing An. aquasalis. Occurrence of a La Niña event in 1988 (wet and cool phase of the El Niño Southern Oscillation) triggered malaria transmission to unusually high levels, consolidating infection in the area, and rendering traditional control efforts useless. We recommend tracking malaria persistence per village and associated risk factors as methods to reduce the cost of malaria control programs.

Metastatic basal cell carcinoma to the lung.

Basal cell carcinoma is a relatively common tumor with an increasing incidence. Despite this, metastatic disease is an extremely rare event. A review of metastatic basal cell carcinoma is presented.

Use of the parenteral antibiotic Ertapenem as short term prophylaxis in bariatric surgery: a pharmaco-kinetic-pharmacodynamic study in class III obese female patients.

BACKGROUND: The objective of this study was to determine the pharmacokinetics-pharmacodynamics (PK/PD) of Ertapenem in extremely obese female patients (Body Mass Index [BMI] ≥ 40 kg/m²) undergoing bariatric surgery. METHODS: Ten patients received 1 g intravenous Ertapenem 0.5 h prior to surgery as short term prophylaxis. Serum Ertapenem concentrations were determined at baseline, at the end of infusion (30 minutes), then at 1, 2, 4, 8, 12 and 24 hours postinfusion. In patients in whom a liver biopsy was necessitated by clinical need, Ertapenem liver concentrations were determined through intraoperative biopsies at 1 and 2 h postadministration. Peritoneal Ertapenem concentrations were determined in drainage fluid samples collected during the 4-8, 8-12, and 12-24 h intervals after Ertapenem administration. A Monte Carlo simulation was performed to estimate the probability of achieving free drug levels above the minimum inhibitory concentration (fT>MIC) for at least 20% and 40% of the dosing interval as PK/PD targets. RESULTS: Peak drug concentration and 24-h area under the concentration-time curve (AUC) were found to be 191.9 ± 37.4 mg/L and 574.3 ± 110.5 mg·h/L, respectively. Ertapenem liver/serum concentration ratios were 6% at 1 h and 5% at 2 h. Drug concentrations in peritoneal fluid were 28.2 ± 6.4 mg/L at 4-8h, declined to 15.2 ± 5.9 at 8-12h and fell further to 4.79 ± 0.2 mg/L at 12-24 h post-administration. The probability to reach the desired PK/PD targets were never reached at any MICs >0.25 µg/mL with a 90% probability. CONCLUSION: Our data suggest that in extremely obese female patients, the standard dose of 1 g i.v. Ertapenem as short term prophylaxis may not provide optimal clinical levels of free drug for prevention of surgical site infections.

Preoperative medication with oral morphine sulphate and postoperative pain.

BACKGROUND: The administration of an analgesic drug prior to nociceptive surgical stimulus could result in a better postoperative pain management. The aim of this study was to evaluate the effect of preoperative oral morphine sulphate on postoperative pain relief. METHODS: Sixty patients undergoing major abdominal surgery were randomly assigned to premedication with 0.5 mg/kg oral morphine sulphate (oral morphine group) or 0.05 mg/kg oral midazolam (active placebo group). Primary outcome was efficacy of morphine premedication on opioid administration of IntraVenous Patient Controlled Analgesia (IVPCA) doses, at 4, 24, and 48 hours after completion of surgery and reducing static and dynamic visual analogue scale (sVAS and dVAS) scores. Secondary outcome was the time needed for the recovery of canalization of the gastro-intestinal tract. It was also evaluated fentanyl intraoperative consumption. Statistical analysis was performed by linear regression and student t test. Values of P<0.05 were considered significant. RESULTS: The two groups were comparable with respect to patient characteristics. At 24 and 48 hours post surgery, administered IVPCA doses were reduced in the oral morphine group compared to the active placebo group (P<0.05). Values of sVAS and dVAS were significantly lower in the oral morphine group compared to the active placebo group at all assessment times (P<0.05). Fentanyl consumption was similar in both groups. Needs of a ketorolac rescue dose was greater in the ap versus the om group (21 patients in the ap vs 9 patients in the om group, P<0.001). Mean gastrointestinal canalization did not significantly differ between groups. CONCLUSIONS: In major abdominal surgery, premedication with oral morphine sulphate produces better postoperative pain control and has an opioid-sparing effect without delaying gastrointestinal canalization time.

Atherosclerosis is enhanced by testosterone deficiency and attenuated by CETP expression in transgenic mice.

In this work, we investigated the impact of testosterone deficiency and cholesteryl ester transfer protein (CETP) expression on lipoprotein metabolism and diet-induced atherosclerosis. CETP transgenic mice and nontransgenic (nTg) littermates were studied 4 weeks after bilateral orchidectomy or sham operation. Castrated mice had an increase in the LDL fraction (+36% for CETP and +79% for nTg mice), whereas the HDL fraction was reduced (-30% for CETP and -11% for nTg mice). Castrated mice presented 1.7-fold higher titers of anti-oxidized LDL (Ox-LDL) antibodies than sham-operated controls. Plasma levels of CETP, lipoprotein lipase, and hepatic lipase were not changed by castration. Kinetic studies showed no differences in VLDL secretion rate, VLDL-LDL conversion rate, or number of LDL and HDL receptors. Competition experiments showed lower affinity of LDL from castrated mice for tissue receptors. Diet-induced atherosclerosis studies showed that testosterone deficiency increased by 100%, and CETP expression reduced by 44%, the size of aortic lesion area in castrated mice. In summary, testosterone deficiency increased plasma levels of apolipoprotein B-containing lipoproteins (apoB-LPs) and anti-OxLDL antibodies, decreased LDL receptor affinity, and doubled the size of diet-induced atherosclerotic lesions. The expression of CETP led to a milder increase of apoB-LPs and reduced atherosclerotic lesion size in testosterone-deficient mice.

Spatial and temporal distribution of anopheline larvae in two malarious areas in Sucre State, Venezuela.

The spatial and temporal distribution of anopheline larvae was studied in two coastal malarious areas of Sucre, State, Venezuela. Seven habitat types were sampled in the village of Guayana and eight species of Anopheles were collected. Anopheles aquasalis was the predominant species collected and was most abundant in the brackish marsh habitat (71 larvae per 100 samples). It was most abundant during the rainy season. At the second location, Santa Fé, six habitat types were sampled and four anopheline species were collected. Habitats where An. aquasalis was most abundant were temporary freshwater ponds (34 larvae per 100 samples) and mangroves (10.5 larvae per 100 samples). At this location it was also most abundant in the rainy season. During the dry season it was collected in small numbers in river pools (1.3 larvae per 100 samples) along with large numbers of An. pseudopunctipennis (479 larvae per 100 samples). Larval control could be an important component of the malaria control program because major habitats could be defined and presence and abundance of larvae was limited to specific times of year.

Adult abundance, biting behavior and parity of Anopheles aquasalis, Curry 1932 in two malarious areas of Sucre State, Venezuela.

The principal vector of malaria in eastern Venezuela, Anopheles aquasalis, is exophagic and exophilic. Control using indoor insecticide house sprays has failed to lower the number of malaria cases. Therefore, studies were initiated in two villages of the eastern coastal state of Sucre to better understand this vector's biology and develop a more integrated control program. An. aquasalis was found to have a crepuscular biting behavior with a major peak at dusk and a minor peak at dawn. Mosquitos were collected more outdoors than indoors. Forty-seven percent of the biting took place before people went to bed (22:30 hr) and 69% of the mosquitos biting during this time period bite outdoors. Outdoor biting could be the reason why indoor spraying alone did not lower malaria cases. Seasonal abundance was greater in the rainy season compared to the dry season. Seasonal parous rates were high (78.3%-100%) and similar indoors and outdoors and between dry and wet season in Santa Fé. In Guayana, the seasonal parity was lower (34.6%-42.2%) than Santa Fé with indoor parity slightly higher than outdoors. Malaria cases were higher in Santa Fé, but adult mosquito density was much lower than in Guayana. This difference could have been due to higher parity in Santa Fé compared to Guayana. The greater distance to the nearest breeding site and presence of alternative hosts in Guayana can not be discounted as factors which contributed to the difference in malaria transmission between locations. We concluded that knowledge on seasonal occurrence, biting activity, resting behavior and breeding site location can be used to design a new control strategy for this vector.