Dapagliflozin reduces the amplitude of shortening and Ca(2+) transient in ventricular myocytes from streptozotocin-induced diabetic rats.

In the management of type 2 diabetes mellitus, Dapagliflozin (DAPA) is a newly introduced selective sodium-glucose co-transporter 2 inhibitor which promotes renal glucose excretion. Little is known about the effects of DAPA on the electromechanical function of the heart. This study investigated the effects of DAPA on ventricular myocyte shortening and intracellular Ca(2+) transport in streptozotocin (STZ)-induced diabetic rats. Shortening, Ca(2+) transients, myofilament sensitivity to Ca(2+) and sarcoplasmic reticulum Ca(2+), and intracellular Ca(2+) current were measured in isolated rats ventricular myocytes by video edge detection, fluorescence photometry, and whole-cell patch-clamp techniques. Diabetes was characterized in STZ-treated rats by a fourfold increase in blood glucose (440 ± 25 mg/dl, n = 21) compared to Controls (98 ± 2 mg/dl, n = 19). DAPA reduced the amplitude of shortening in Control (76.68 ± 2.28 %, n = 37) and STZ (76.58 ± 1.89 %, n = 42) ventricular myocytes, and reduced the amplitude of the Ca(2+) transients in Control and STZ ventricular myocytes with greater effects in STZ (71.45 ± 5.35 %, n = 16) myocytes compared to Controls (92.01 ± 2.72 %, n = 17). Myofilament sensitivity to Ca(2+) and sarcoplasmic reticulum Ca(2+) were not significantly altered by DAPA in either STZ or Control myocytes. L-type Ca(2+) current was reduced in STZ myocytes compared to Controls and was further reduced by DAPA. In conclusion, alterations in the mechanism(s) of Ca(2+) transport may partly underlie the negative inotropic effects of DAPA in ventricular myocytes from STZ-treated and Control rats.

Effects of a sucrose-enriched diet on the pattern of gene expression, contraction and Ca(2+) transport in Goto-Kakizaki type 2 diabetic rat heart.

There has been a spectacular rise in the global prevalence of type 2 diabetes mellitus (T2DM), and cardiovascular disease is the major cause of morbidity and mortality in diabetic patients. A variety of diastolic and systolic dysfunctions have been demonstrated in type 2 diabetic heart. The consumption of sugar-sweetened beverages has been linked to rising rates of obesity, which in turn is a risk factor for development of T2DM. In this study, the effects of a sucrose-enriched diet on the pattern of gene expression, contraction and Ca(2+) transport in the Goto-Kakizaki T2DM rat heart were investigated. Genes encoding cardiac muscle proteins (Myh7, Mybpc3, Myl1, Myl3 and Mylpf), intercellular proteins (Gja4), cell membrane transport (Atp1b1), calcium channels (Cacna1c, Cacna1g and Cacnb1) and potassium channels (Kcnj11) were upregulated and genes encoding potassium channels (Kcnb1) were downregulated in GK compared with control rats. Genes encoding cardiac muscle proteins (Myh6, Mybpc3 and Tnn2), intercellular proteins (Gja1 and Gja4), intracellular Ca(2+) transport (Atp2a1 and Ryr2), cell membrane transport (Atp1a2 and Atp1b1) and potassium channel proteins (Kcnj2 and Kcnj8) were upregulated and genes encoding cardiac muscle proteins (Myh7) were downregulated in control rats fed sucrose compared with control rats. Genes encoding cardiac muscle proteins (Myh7) and potassium channel proteins (Kcnj11) were downregulated in control and GK rats fed sucrose compared with control and GK rats, respectively. The amplitude of shortening was reduced in myocytes from the control-sucrose group compared with control rats and in the GK-sucrose group compared with GK rats. The amplitude of the Ca(2+) transient was increased in myocytes from control-sucrose compared with control rats and decreased in GK-sucrose compared with GK rats. Subtle alterations in the pattern of expression of genes encoding a variety of cardiac muscle proteins are associated with changes in shortening and intracellular Ca(2+) transport in ventricular myocytes from GK T2DM and control rats fed a sucrose-enriched diet.

Effects of exercise training on excitation-contraction coupling and related mRNA expression in hearts of Goto-Kakizaki type 2 diabetic rats.

Although, several novel forms of intervention aiming at newly identified therapeutic targets are currently being developed for diabetes mellitus (DM), it is well established that physical exercise continues to be one of the most valuable forms of non-pharmacological therapy. The aim of the study was to investigate the effects of exercise training on excitation-contraction coupling and related gene expression in the Goto-Kakizaki (GK) type 2 diabetic rat heart and whether exercise is able to reverse diabetes-induced changes in excitation-contraction coupling and gene expression. Experiments were performed in GK and control rats aged 10-11 months following 2-3 months of treadmill exercise training. Shortening, [Ca(2+)]i and L-type Ca(2+) current were measured in ventricular myocytes with video edge detection, fluorescence photometry and whole cell patch clamp techniques, respectively. Expression of mRNA was assessed in ventricular muscle with real-time RT-PCR. Amplitude of shortening, Ca(2+) transients and L-type Ca(2+) current were not significantly altered in ventricular myocytes from GK sedentary compared to control sedentary rats or by exercise training. Expression of mRNA encoding Tpm2, Gja4, Atp1b1, Cacna1g, Cacnb2, Hcn2, Kcna3 and Kcne1 were up-regulated and Gja1, Kcnj2 and Kcnk3 were down-regulated in hearts of sedentary GK rats compared to sedentary controls. Gja1, Cav3 and Kcnk3 were up-regulated and Hcn2 was down-regulated in hearts of exercise trained GK compared to sedentary GK controls. Ventricular myocyte shortening and Ca(2+) transport were generally well preserved despite alterations in the profile of expression of mRNA encoding a variety of cardiac muscle proteins in the adult exercise trained GK diabetic rat heart.

Analysis of human rabies deaths reported at two hospitals in Karachi, Pakistan: a call to save lives by reforming rabies prevention facilities.

BACKGROUND: Rabies is endemic in low- and middle-income countries. It is caused mainly by the bite of a rabid dog and is fatal if not treated effectively and in a timely manner with quality post-exposure prophylaxis. Despite a profusion of private and public healthcare centres in Sindh province, most are ill-equipped to treat dog bites. METHODS: We analysed 129 human deaths from rabies who presented at the emergency departments of two tertiary care hospitals in Karachi over 10 y. Demographic data, time, location of the bite and distance travelled to report symptoms of rabies were recorded. RESULTS: Most victims were male, and children were more often affected; almost none had received post-exposure prophylaxis. A total of 12% of bites were on the face, head or neck. The mean incubation period was 56 d. Most (60%) of the rabies victims travelled long distances, hoping to receive treatment. CONCLUSIONS: Rabies deaths were either due to a lack of awareness or the non-availability of rabies immunobiologicals within easy reach. Public health services must raise awareness, conduct surveillance and provide appropriately spaced centres for free treatment of dog bites. This lethal disease must be prevented at all costs.

Shortening and intracellular Ca2+ in ventricular myocytes and expression of genes encoding cardiac muscle proteins in early onset type 2 diabetic Goto-Kakizaki rats.

There has been a spectacular rise in the global prevalence of type 2 diabetes mellitus. Cardiovascular complications are the major cause of morbidity and mortality in diabetic patients. Contractile dysfunction, associated with disturbances in excitation-contraction coupling, has been widely demonstrated in the diabetic heart. The aim of this study was to investigate the pattern of cardiac muscle genes that are involved in the process of excitation-contraction coupling in the hearts of early onset (8-10 weeks of age) type 2 diabetic Goto-Kakizaki (GK) rats. Gene expression was assessed in ventricular muscle with real-time RT-PCR; shortening and intracellular Ca(2+) were measured in ventricular myocytes with video edge detection and fluorescence photometry, respectively. The general characteristics of the GK rats included elevated fasting and non-fasting blood glucose and blood glucose at 120 min following a glucose challenge. Expression of genes encoding cardiac muscle proteins (Myh6/7, Mybpc3, Myl1/3, Actc1, Tnni3, Tnn2, Tpm1/2/4 and Dbi) and intercellular proteins (Gja1/4/5/7, Dsp and Cav1/3) were unaltered in GK ventricle compared with control ventricle. The expression of genes encoding some membrane pumps and exchange proteins was unaltered (Atp1a1/2, Atp1b1 and Slc8a1), whilst others were either upregulated (Atp1a3, relative expression 2.61 ± 0.69 versus 0.84 ± 0.23) or downregulated (Slc9a1, 0.62 ± 0.07 versus 1.08 ± 0.08) in GK ventricle compared with control ventricle. The expression of genes encoding some calcium (Cacna1c/1g, Cacna2d1/2d2 and Cacnb1/b2), sodium (Scn5a) and potassium channels (Kcna3/5, Kcnj3/5/8/11/12, Kchip2, Kcnab1, Kcnb1, Kcnd1/2/3, Kcne1/4, Kcnq1, Kcng2, Kcnh2, Kcnk3 and Kcnn2) were unaltered, whilst others were either upregulated (Cacna1h, 0.95 ± 0.16 versus 0.47 ± 0.09; Scn1b, 1.84 ± 0.16 versus 1.11 ± 0.11; and Hcn2, 1.55 ± 0.15 versus 1.03 ± 0.08) or downregulated (Hcn4, 0.16 ± 0.03 versus 0.37 ± 0.08; Kcna2, 0.35 ± 0.03 versus 0.80 ± 0.11; Kcna4, 0.79 ± 0.25 versus 1.90 ± 0.26; and Kcnj2, 0.52 ± 0.07 versus 0.78 ± 0.08) in GK ventricle compared with control ventricle. The amplitude of ventricular myocyte shortening and the intracellular Ca(2+) transient were unaltered; however, the time-to-peak shortening was prolonged and time-to-half decay of the Ca(2+) transient was shortened in GK myocytes compared with control myocytes. The results of this study demonstrate changes in expression of genes encoding various excitation-contraction coupling proteins that are associated with disturbances in myocyte shortening and intracellular Ca(2+) transport.

Contractility of ventricular myocytes is well preserved despite altered mechanisms of Ca2+ transport and a changing pattern of mRNA in aged type 2 Zucker diabetic fatty rat heart.

There has been a spectacular rise in the global prevalence of type 2 diabetes mellitus and cardiovascular complications are the major cause of morbidity and mortality in diabetic patients. The objective of the study was to investigate ventricular myocyte shortening, intracellular Ca(2+) signalling and expression of genes encoding cardiac muscle proteins in the aged Zucker diabetic fatty (ZDF) rat. There was a fourfold elevation in non-fasting blood glucose in ZDF rats (478.43 ± 29.22 mg/dl) compared to controls (108.22 ± 2.52 mg/dl). Amplitude of shortening, time to peak (TPK) and time to half (THALF) relaxation of shortening were unaltered in ZDF myocytes compared to age-matched controls. Amplitude and THALF decay of the Ca(2+) transient were unaltered; however, TPK Ca(2+) transient was prolonged in ZDF myocytes (70.0 ± 3.2 ms) compared to controls (58.4 ± 2.3 ms). Amplitude of the L-type Ca(2+) current was reduced across a wide range of test potentials (-30 to +40 mV) in ZDF myocytes compared to controls. Sarcoplasmic reticulum Ca(2+) content was unaltered in ZDF myocytes compared to controls. Expression of genes encoding cardiac muscle proteins, membrane Ca(2+) channels, and cell membrane ion transport and intracellular Ca(2+) transport proteins were variously altered. Myh6, Tnnt2, Cacna2d3, Slc9a1, and Atp2a2 were downregulated while Myl2, Cacna1g, Cacna1h, and Atp2a1 were upregulated in ZDF ventricle compared to controls. The results of this study have demonstrated that preserved ventricular myocyte shortening is associated with altered mechanisms of Ca(2+) transport and a changing pattern of genes encoding a variety of Ca(2+) signalling and cardiac muscle proteins in aged ZDF rat.

Changing pattern of gene expression is associated with ventricular myocyte dysfunction and altered mechanisms of Ca2+ signalling in young type 2 Zucker diabetic fatty rat heart.

The association between type 2 diabetes and obesity is very strong, and cardiovascular complications are the major cause of morbidity and mortality in diabetic patients. The aim of this study was to investigate early changes in the pattern of genes encoding cardiac muscle regulatory proteins and associated changes in ventricular myocyte contraction and Ca(2+) transport in young (9- to 13-week-old) type 2 Zucker diabetic fatty (ZDF) rats. The amplitude of myocyte shortening was unaltered; however, time-to-peak shortening and time to half-relaxation of shortening were prolonged in ZDF myocytes (163 ± 5 and 127 ± 7 ms, respectively) compared with age-matched control rats (136 ± 5 and 103 ± 4 ms, respectively). The amplitude of the Ca(2+) transient was unaltered; however, time-to-peak Ca(2+) transient was prolonged in ZDF myocytes (66.9 ± 2.6 ms) compared with control myocytes (57.6 ± 2.3 ms). The L-type Ca(2+) current was reduced, and inactivation was prolonged over a range of test potentials in ZDF myocytes. At 0 mV, the density of L-type Ca(2+) current was 1.19 ± 0.28 pA pF(-1) in ZDF myocytes compared with 2.42 ± 0.40 pA pF(-1) in control myocytes. Sarcoplasmic reticulum Ca(2+) content, release and uptake and myofilament sensitivity to Ca(2+) were unaltered in ZDF myocytes compared with control myocytes. Expression of genes encoding various L-type Ca(2+) channel proteins (Cacna1c, Cacna1g, Cacna1h and Cacna2d1) and cardiac muscle proteins (Myh7) were upregulated, and genes encoding intracellular Ca(2+) transport regulatory proteins (Atp2a2 and Calm1) and some cardiac muscle proteins (Myh6, Myl2, Actc1, Tnni3, Tnn2, and Tnnc1) were downregulated in ZDF heart compared with control heart. A change in the expression of genes encoding myosin heavy chain and L-type Ca(2+) channel proteins might partly underlie alterations in the time course of contraction and Ca(2+) transients in ventricular myocytes from ZDF rats.

New results with the Zenith graft in the treatment of aortic aneurysms.

Aneurysmal disease of the arterial vasculature has been reported since ancient times. Regarding aneurysms of the aorta, a steady progress has been made ranging from making such pathology amenable to surgical treatment to making the procedure much less invasive. There have been a number of stent grafts, introduced by different companies, used to exclude different segments of the aneurysmal aorta and the Zenith devices are one of them. The safety and efficacy of these devices to exclude infrarenal and descending thoracic aortic aneurysms has been well documented. The early and late complications associated with these procedures and the methods used to manage such complications have also been elucidated in different publications. In dealing with pararenal and thoracoabdominal aneurysms, the need to ensure patency of the visceral vessels while still repairing the aorta to healthy tissue must be considered. Strategies involving fenestrations and side-arm branches have evolved extending the ability to treat the entire aorta with an endovascular approach. Challenges exist including the inherent tortuosity and mobility of the aortic arch, close approximation of the supra-aortic vessels, small or multiple renal vessels, the commonly noted arcuate ligament compression of the celiac artery, but great strides have been made and virtually all pathologies have been addressed. The desire for smaller delivery systems has spurred interest in low-profile devices. This manuscript is intended to address the latest developments and clinical results for endovascular grafting of the aorta.

Altered gene expression may underlie prolonged duration of the QT interval and ventricular action potential in streptozotocin-induced diabetic rat heart.

Ventricular electrical conduction has been investigated in the streptozotocin (STZ)-induced diabetic rat. Diabetes was induced with a single injection of STZ (60 mg/kg bodyweight, ip). The ECG was measured continuously, in vivo, using a biotelemetry system. Left ventricular action potentials were recorded with an extracellular suction electrode. Expression of mRNA transcripts for selected ion transport proteins was measured in left ventricle with real-time RT-PCR. At 10 weeks after STZ treatment, in vivo heart rate (HR) was reduced (267 +/- 3 vs. 329 +/- 5 BPM), QRS complex duration and QT interval were prolonged in diabetic rats compared to controls. In vitro spontaneous HR was reduced and paced heart action potential repolarization was prolonged in diabetic rats compared to controls. The mRNA expression for Kcnd2 (I (to) channel) and Kcne2 (I (kr) channel) was significantly reduced in diabetic rats compared to controls. Altered gene expression and, in particular, genes that encode K(+) channel proteins may underlie delayed propagation of electrical activity in the ventricular myocardium of STZ-induced diabetic rat.

Calcium Signaling in the Ventricular Myocardium of the Goto-Kakizaki Type 2 Diabetic Rat.

The association between diabetes mellitus (DM) and high mortality linked to cardiovascular disease (CVD) is a major concern worldwide. Clinical and preclinical studies have demonstrated a variety of diastolic and systolic dysfunctions in patients with type 2 diabetes mellitus (T2DM) with the severity of abnormalities depending on the patients' age and duration of diabetes. The cellular basis of hemodynamic dysfunction in a type 2 diabetic heart is still not well understood. The aim of this review is to evaluate our current understanding of contractile dysfunction and disturbances of Ca2+ transport in the Goto-Kakizaki (GK) diabetic rat heart. The GK rat is a widely used nonobese, nonhypertensive genetic model of T2DM which is characterized by insulin resistance, elevated blood glucose, alterations in blood lipid profile, and cardiac dysfunction.

The Pattern of mRNA Expression Is Changed in Sinoatrial Node from Goto-Kakizaki Type 2 Diabetic Rat Heart.

BACKGROUND: In vivo experiments in Goto-Kakizaki (GK) type 2 diabetic rats have demonstrated reductions in heart rate from a young age. The expression of genes encoding more than 70 proteins that are associated with the generation and conduction of electrical activity in the GK sinoatrial node (SAN) have been evaluated to further clarify the molecular basis of the low heart rate. MATERIALS AND METHODS: Heart rate and expression of genes were evaluated with an extracellular electrode and real-time RT-PCR, respectively. Rats aged 12-13 months were employed in these experiments. RESULTS: Isolated spontaneous heart rate was reduced in GK heart (161 ± 12 bpm) compared to controls (229 ± 11 bpm). There were many differences in expression of mRNA, and some of these differences were of particular interest. Compared to control SAN, expression of some genes were downregulated in GK-SAN: gap junction, Gja1 (Cx43), Gja5 (Cx40), Gjc1 (Cx45), and Gjd3 (Cx31.9); cell membrane transport, Trpc1 (TRPC1) and Trpc6 (TRPC6); hyperpolarization-activated cyclic nucleotide-gated channels, Hcn1 (HCN1) and Hcn4 (HCN4); calcium channels, Cacna1d (Cav1.3), Cacna1g (Cav3.1), Cacna1h (Cav3.2), Cacna2d1 (Cavα2δ1), Cacna2d3 (Cavα2δ3), and Cacng4 (Cav γ 4); and potassium channels, Kcna2 (Kv1.2), Kcna4 (Kv1.4), Kcna5 (Kv1.5), Kcnb1 (Kv2.1), Kcnd3 (Kv4.3), Kcnj2 (Kir2.1), Kcnk1 (TWIK1), Kcnk5 (K2P5.1), Kcnk6 (TWIK2), and Kcnn2 (SK2) whilst others were upregulated in GK-SAN: Ryr2 (RYR2) and Nppb (BNP). CONCLUSIONS: This study provides new insight into the changing expression of genes in the sinoatrial node of diabetic heart.

Comparison of the performance of 1966- versus 2003-type turkeys when fed representative 1966 and 2003 turkey diets: growth rate, livability, and feed conversion.

Body weight, livability, and feed conversion of a randombred control turkey line (RBC2) started in 1966 at The Ohio State University was compared with that of modern commercial turkeys hatched in 2003 when fed representative 1966- and 2003-type diets from hatch (March 5, 2003) through 196 d of age. Each pen of modern turkeys consisted of 5 birds each of the Nicholas, British United Turkeys of America, and Hybrid strains. Eight groups (i.e., 2 strains (RBC2 vs. modern), 2 sexes, and 2 dietary regimens) were randomly assigned into each of 4 blocks of 8 litter floor pens (32 total) for growout. Using the BW performance of the 2 strains on the modern feed as the basis, the study showed that the 2003 turkeys were approximately twice as heavy as the 1966 RBC2 at the 4 slaughter ages and that tom weights have increased by 186, 208, 227, and 241 g/yr, and hen weights have increased by 164, 179, 186, and 205 g/yr at 112, 140, 168, and 196 d of age, respectively, over the past 37 yr. Cumulative feed conversion (kg of feed/kg of BW) was approximately 20% better in the 2003 tom turkey on the 2003 feed (2.638) than in the RBC2 tom on the 1966 feed (3.278) at 20 wk of age. Feed efficiency to 11 kg of BW in the 2003 toms (2.132 at 98 d of age) was approximately 50% better than in the RBC2 toms (4.208 at 196 d of age). The number of days to reach that weight was halved during this period of time. Growth performance during the different periods of the study appeared to be strongly affected by type of feed used and seasonal changes in ambient temperature. Overall livability was very good for all groups, but the mortality level of the RBC2 was consistently higher, although not significantly so, than for the modern birds.

A comparison of the immune response of 2003 commercial turkeys and a 1966 randombred strain when fed representative 2003 and 1966 turkey diets.

The immunological performance of modern turkeys (one-third each of the Nicholas Turkey, British United Turkeys of America, and Hybrid Turkey strains) hatched in 2003 (2003 strain) was compared with that of a randombred control turkey strain (RBC2) established in calendar year 1966, when fed representative 1966 and 2003 type diets. The 2003 strain had a higher BW and bursa of Fabricius weight relative to total BW compared with the RBC2 strain (P = 0.0001) when measured at 12 and 13 d of age, respectively. Total antibody response against SRBC did not differ between strains, nor were any differences observed in the IgM antibody levels either during a primary or secondary SRBC challenge. However, RBC2 poults had higher IgG levels (P = 0.02) than the 2003 strain at 7 d post secondary SRBC challenge. No significant differences were observed in the phytohemagglutinin phosphate-mediated toe-web lymphoblastic response. However, the 2003-strain turkeys seemed to have a better swelling response (P = 0.06) than the RBC2-strain turkeys when measured at 24 h post phytohemagglutinin phosphate injection. The modern turkeys also had higher mononuclear phagocytic system function, as measured by clearance of carbon particles from the bloodstream 5 min post intravenous injection of colloidal carbon (P = 0.02). These results indicate that selection over the years of turkeys for improved performance traits has had no adverse effects on most of the immune system indicators when examined prior to sexual maturity in the current study.

Conservation of avian genetic resources: current opportunities and challenges--a summary.

Presented is an overview of the thesis of this symposium with a snapshot summation of the papers presented, including modest critiques and suggestions for future efforts.

Differentiation properties of avian tumor cell lines: analysis using chicken fetal antigen and other markers.

Three avian lymphoblastoid tumor cell lines were compared for the expression of the serologically complex cell surface antigen, chicken fetal antigen (CFA), and other properties associated with differentiation. Two Marek's disease cell lines (CU-12 and CU-36) and a cell line associated with lymphoid leukosis (CU-10) were all found to differ qualitatively in the expression of CFA. While both Marek's disease cell lines exhibited overall phenotypes similar to those of T-lymphocytes, the lymphoid leukosis cell line possessed characteristics in common with either immature lymphocytes or cells of the reticuloendothelial system. The specific patterns of CFA expression on these lymphoid tumor cells may be related to the particular level of differentiation blockage during tumorigenesis as has been proposed for erythroblastosis. The lymphoid leukosis cell line exhibited a pattern of CFA expression that would not distinguish between the possibility of differentiation blockage versus retrogenic expression. Since CFA is known to be associated with a series of cell surface glycoproteins, the exact relationship between individual molecules, the level of lymphoid differentiation, and changes associated with tumorigenesis may now be examined.

Reduction in the amplitude of shortening and Ca(2+) transient by phlorizin and quercetin-3-O-glucoside in ventricular myocytes from streptozotocin-induced diabetic rats.

Diabetes mellitus is the leading cause of cardiovascular morbidity and mortality. Phlorizin (PHLOR) and quercetin-3-O-glucoside (QUER-3-G) are two natural compounds reported to have antidiabetic properties by inhibiting sodium/glucose transporters. Their effects on ventricular myocyte shortening and intracellular Ca(2+) in streptozotocin (STZ)-induced diabetic rats were investigated. Video edge detection and fluorescence photometry were used to measure ventricular myocyte shortening and intracellular Ca(2+), respectively. Blood glucose in STZ rats was 4-fold higher (469.64+/-22.23 mg/dl, n=14) than in Controls (104.06+/-3.36 mg/dl, n=16). The amplitude of shortening was reduced by PHLOR in STZ (84.76+/-2.91 %, n=20) and Control (83.72+/-2.65 %, n=23) myocytes, and by QUER-3-G in STZ (79.12+/-2.28 %, n=20) and Control (76.69+/-1.92 %, n=30) myocytes. The amplitude of intracellular Ca(2+) was also reduced by PHLOR in STZ (82.37+/-3.16 %, n=16) and Control (73.94+/-5.22 %, n=21) myocytes, and by QUER-3-G in STZ (73.62+/-5.83 %, n=18) and Control (78.32+/-3.54 %, n=41) myocytes. Myofilament sensitivity to Ca(2+) was not significantly altered by PHLOR; however, it was reduced by QUER-3-G modestly in STZ myocytes and significantly in Controls. PHLOR and QUER-3-G did not significantly alter sarcoplasmic reticulum Ca(2+) in STZ or Control myocytes. Altered mechanisms of Ca(2+) transport partly underlie PHLOR and QUER-3-G negative inotropic effects in ventricular myocytes from STZ and Control rats.

Anorectal anomalies in adult females corrected by posterior sagittal anorectoplasty.

Posterior sagittal anorectoplasty (PSARP) is preferred by most pediatric surgeon and intermediate types of anorectal anomalies (ARA) in infants. In this report, we describe two girls who presented in their late teens with ARA and were treated by PSARP. Prior to this report, only two adult females with congenital rectovaginal fistulae treated by PSARP have been reported. Megarectum is a feature in late presentation of ARA and requires rectal tapering during PSARP. The functional outcome in late presentation of ARA is discussed.

Avian macrophage: effector functions in health and disease.

Monocytes-macrophages, cells belonging to the mononuclear phagocytic system, are considered as the first line of immunological defense. Being mobile scavenger cells, macrophages participate in innate immunity by serving as phagocytic cells. These cells arise in the bone marrow and subsequently enter the blood circulation as blood monocytes. Upon migration to various tissues, monocytes mature and differentiate into tissue macrophages. Macrophages then initiate the 'acquired' immune response in their capacity as antigen processing and presenting cells. While responding to their tissue microenvironment or exogenous antigenic challenge, macrophages may secrete several immunoregulatory cytokines or metabolites. Being the first line of immunological defense, macrophages therefore represent an important step during interaction with infectious agents. The outcome of the macrophage-pathogen interaction depends upon several factors including the stage of macrophage activation, the nature of the infectious agent, the level of genetic control on macrophage function as well as environmental and nutritional factors that may modulate macrophage activation and functions. Research in avian macrophages has lagged behind that in mammals. This has been largely due to the lack of harvestable resident macrophages from the chicken peritoneal cavity. However, the development of elicitation protocols to harvest inflammatory abdominal macrophages and the availability of transformed chicken macrophage cell lines, has enabled researchers to address several questions related to chicken macrophage biology and function in health and disease. In this manuscript the basic profiles of several macrophage effector functions are described. In addition, the interaction of macrophages with various pathogens as well as the effect of genetic and environmental factors on macrophage functional modulation is described.

Effects of AFB1 embryonic exposure on chicken mononuclear phagocytic cell functions.

Effects of embryonic exposure to aflatoxin-B1 (AFB1) on the postnatal development of chicken mononuclear phagocytic system function was examined. Single exposure of 6-d chick embryos to 0.1, 0.5, and 1 micrograms AFB1 in 10 microL acetone was employed. Control embryos received 10 microliters solvent and sham-treated controls included embryos with a hole in the egg shell with no compound added. Aflatoxin B1 exposure caused a dose-related increase in embryonic mortality. After hatch, no differences were observed in body weight gain among treatment groups. The incidence of circulating thrombocytes was reduced in chicks exposed to the highest AFB1 dose with enhancement in monocyte and lymphocyte cell populations. Birds exposed to 1 microgram AFB1 recruited fewer macrophages in the peritoneal cavity after i.p. Sephadex elicitation along with reduced substrate adherence potential of peritoneal exudate cells. Similarly, macrophages from 0.5 and 1 micrograms AFB1-treated birds had depressed phagocytic potential. These results suggest that long-term immune depression of macrophage-mediated functions can occur following embryonic exposure to AFB1.

Identification and production of monoclonal antibodies against a discriminating protein molecule between B and D variants of encephalomyocarditis virus.

The protein profiles of two EMC virus variants B and D in the infected L929 fibroblast lysates were examined using one- and two-dimensional gel electrophoresis. Both variants yielded a protein molecule of similar molecular weight but differing in its isoelectric point (pI). The B variant lysate yielded a molecule with pI congruent to 7.5 whereas the same molecule from the D lysate focused at pI congruent to 5.2. A monoclonal antibody (MCA) produced against pI congruent to 5.2 fraction of the D variant successfully detected viral antigens in the D variant infected fibroblasts with only background cross reactivity with the B variant infected cells. This MCA also detected D viral antigen(s) in organ sections obtained from D but not from B variant infected mice. This study therefore suggests a clear shift in the pI of a 23 kD protein molecule serving as a possible discriminating antigen between the B and D variants of EMC virus.