Richard M Whitehurst

T-Type Calcium Channels Facilitate Insulin Secretion by Enhancing General Excitability in the Insulin-Secreting β-Cell Line, INS-11

The present study addresses the function of T-type voltage-gated calcium channels in insulin-secreting cells. We used whole-cell voltage and current recordings, capacitance measurements, and RIA techniques to determine the contribution of T-type calcium channels in modulation of electrical activity and in stimulus-secretion coupling in a rat insulin secreting cell line, INS-1. By employing a double pulse protocol in the current-clamp mode, we found that activation of T-type calcium channels provided a low threshold depolarizing potential that decreased the latency of onset of action potentials and furthermore increased the frequency of action potentials, both of which are abolished by administration of nickel chloride (NiCl2), a selective T-type calcium channel blocker. Moreover application of high frequency stimulation, as compared with low frequency stimulation, caused a greater change in membrane capacitance (ΔCm), suggesting higher insulin secretion. We demonstrated that glucose stimulated insulin sec...

T-type Ca2+ channels are involved in high glucose-induced rat neonatal cardiomyocyte proliferation.

Infants develop hypertrophic cardiomyopathy in ≈30% of diabetic pregnancies. We have characterized the effects of glucose on voltage-gated T-type Ca2+ channels and intracellular free calcium concentration, [Ca2+]i in neonatal rat cardiomyocytes. We found that T-type Ca2+ channel current density increased significantly in primary culture neonatal cardiac myocytes that were treated with 25 mM glucose for 48 h when compared with those that were treated with 5 mM glucose. High-glucose treatment also caused a higher Ca2+ influx elicited by 50 mM KCl in the myocytes. KCl-induced Ca2+ influx was attenuated when nickel was present. Real-time PCR studies demonstrated that mRNA levels of both α1G (Cav3.1) and α1H (Cav3.2) T-type Ca2+ channels were elevated after high-glucose treatment. High-glucose also significantly increased ventricular cell proliferation as well as the proportion of cells in the S-phase of the cell cycle; both effects were reversed by nickel or mibefradil. These results indicate that high glucose causes a rise in [Ca2+]i in neonatal cardiac myocytes by a mechanism that is associated with the regulation of the T-type Ca2+ channel activity.

Delayed Cord Clamping in Preterm Neonates: A Review of Benefits and Risks.

Importance Delayed clamping of the umbilical cord of premature neonates decreases perinatal morbidity. Allowing time for autotransfusion of placental blood before the umbilical cord is clamped represents a simple practice that may have significant impact. In light of many professional societies recommending delayed cord clamping in premature neonates because of its beneficial effects, the topic still holds many unanswered questions. Objective The purpose of this article is to review the most recent evidence available regarding delayed cord clamping in premature neonates. Evidence Acquisition A literature search using PubMed, Cochrane database, and cumulative index of nursing and allied health literature provided the references for this review. Results Although the evidence comes primarily from small trials, delayed umbilical cord clamping in premature neonates is associated with less need for red blood cell transfusions, increase in hemoglobin and hematocrit levels, and decrease in risk of intraventricular hemorrhage and necrotizing enterocolitis. No maternal or neonatal risks have been demonstrated. Data on long-term outcomes are lacking. Conclusions and Relevance Delayed cord clamping in premature neonates is a simple procedure that the current evidence supports to improve neonatal morbidity. The impact on long-term outcomes remains limited. The optimal time to delay cord clamping and potential risks are poorly studied. Target Audience Obstetricians and gynecologists, family physicians. Learning Objectives After completing this activity, the learner will be better able to: review the most current, available evidence of the topic of delayed cord clamping in premature neonates; learn the benefits that have been demonstrated to decrease morbidity of premature neonates exposed to delayed cord clamping; discuss the potential risks of delayed cord clamping and clinical scenarios that may predispose the infant to these risks; and identify what still remains unknown about the risks and benefits of delayed cord clamping in premature neonates.

Pleural effusion as a complication of a remotely placed catheter in a preterm infant

CASE PRESENTATION A newborn female infant, born at 29 weeks of gestation, was delivered via caesarian section for fetal heart rate decelerations and suspected chorioamnionitis. She weighed 1460 g. Her mother was a 39-year-old African American who recently had 17% total body burn. She was being treated with vancomycin and ceftriaxone. The mother’s prenatal labs were within normal limits. Infant’s Apgar scores were 7 and 9 at 1 and 5 min after birth, respectively. She subsequently developed an increase in work of breathing that required the use of nasal continuous positive airway pressure (NCPAP). Antibiotics (ampicillin and ceftazidime) were started on admission. The infant was intubated at 10 h of life and was given surfactant for respiratory distress syndrome. An umbilical arterial catheter (UAC) was placed for blood sampling, blood pressure monitoring, and infusion of total parenteral nutrition (TPN). Placement of an umbilical venous catheter was not attempted. At 22 h of age, the infant was extubated and placed back on NCPAP with an oxygen concentration of 21%. On day of life (DOL) 3, the UAC was removed and a peripherally inserted central catheter (PICC) was placed (Figure 1a) in order to continue TPN while progressively increasing her enteral nutrition. On DOL 6, she developed a sudden increase in work of breathing and a rise in oxygen requirement, up to 71%. The infant was reintubated. A plain X-ray image of the chest and abdomen revealed a large right pleural effusion with midline shift (Figure 1b). In addition, when compared to the last X-ray film obtained at the time of the placement of the PICC (DOL3), it was found that the catheter’s tip had migrated from the right external iliac vein to a location at the level of the 12th thoracic vertebrae (T12). A thoracocentesis was performed. Cytopathological analysis of the pleural fluid revealed 22 nucleated cells per ml (22 10 cells per l; mesothelial cells 32% (0.32), neutrophils 29% (0.29), lymphocytes 22% (0.22) and macrophages 17% (0.17)) and 2690 red blood cells per ml (2.7 10 cells per l). Chemical analysis revealed pleural fluid levels of glucose at 704 mg dl 1 (39.1 mmol l ), lactate dehydrogenase (LDH) at 21U l 1 (0.35 mkat l ), protein at o2 g dl 1 (o20 g l ) and triglycerides at 27 mg dl 1 (0.3 mmol l ). Blood glucose levels remained in the

Reducing antibiotic utilization rate in preterm infants: a quality improvement initiative

BackgroundJudicious use of antibiotic therapy in preterm infants is necessary as prolonged and unwarranted use of antibiotics have been associated with adverse short-term and long-term outcomes.Local problemOur baseline data review revealed overuse and unnecessary prolonged antibiotic exposure among preterm infants despite a low suspicion for sepsis.Methods and interventionsThe baseline overall AUR was calculated retrospectively from our pharmacy database for a period of 4 months prior to the quality improvement (QI) initiative (pre-QI phase). The principal QI intervention included the development and implementation of guidance algorithms for evaluation and management of suspected sepsis incorporating key QI measures, such as an emphasis on early discontinuation of antibiotics by 36 h if blood culture remained negative and the introduction of multiplex polymerase chain reaction assay for early identification of causative organisms. This QI initiative was implemented through multiple Plan-Do-Study-Act cycles, starting in February 2016 (QI phase), with an objective to achieve a 10% reduction in the baseline overall AUR by December 2016, in preterm infants with gestational ages between 250/7 and 336/7 weeks. Data for the QI phase of the study were collected prospectively.ResultThe overall AUR (outcome measure) decreased from 154.8 to 138.4 days of treatment per 1000 hospital days (10.6% decrease, p < 0.05) over the 11-month period. However, the overall rate of adherence to guidance algorithm (process measure) remained below the target goal of 90%.ConclusionThis multiphase QI initiative was able to reduce the overall AUR at our NICU. The beneficial impact of this decrease in AUR in preterm infants remains to be determined.

High Glucose Increases [Ca2+]i through an Increased Expression of T-Type Ca2+ Channels in Neonatal Rat Cardiomyocytes

High Glucose Increases [Ca 2+ ] i through an Increased Expression of T-Type Ca 2+ Channels in Neonatal Rat Cardiomyocytes

Pulmonary Administration of Prostacyclin (PGI2) during Partial Liquid Ventilation (PLV) in an Animal Model of Pulmonary Hypertension (PHT) |[dagger]| 1662

Pulmonary Administration of Prostacyclin (PGI 2 ) during Partial Liquid Ventilation (PLV) in an Animal Model of Pulmonary Hypertension (PHT) † 1662

Inhaled Nitric Oxide (iNO) and Inhaled Prostacyclin (iPGI 2 ) in an Animal Model of Pulmonary Hypertension (PHT) : Compared Efficacy and Synergy † 1661

Inhaled Nitric Oxide (iNO) and Inhaled Prostacyclin (iPGI 2 ) in an Animal Model of Pulmonary Hypertension (PHT) : Compared Efficacy and Synergy † 1661

Dexamethasone Increases Calcium Channel Current Density in Neonatal Rat Primary Cultured Myocytes • 147

Dexamethasone Increases Calcium Channel Current Density in Neonatal Rat Primary Cultured Myocytes • 147

EFFICACY OF INHALED NITRIC OXIDE (iNO) AND ALKALOSIS DURING PARTIAL LIQUID VENTILATION IN PULMONARY HYPERTENSION. |[dagger]| 1495

We investigated the efficacy of the prevailing therapies for pulmonary hypertension when combined with partial liquid ventilation (PLV). 36 piglets(age: 7-24 days) were randomly allocated to conventional ventilation (IPPV) or PLV (initial perfluorocarbon volume: 30ml/kg; Rimar 101™) at an Fi02of 0.4. Pulmonary vascular resistance (PVR) was then increased from 51 ± 4 to 189 ± 10 mm Hg/L/ min/kg by infusion of a thromboxane(TX) mimetic (U46,619: 0.09 ± 0.01 μg/kg/min). Animals were sequentially tested under: eucapnea (EU) iNO 5ppm iNO 40 ppmeucapnea respiratory alkalosis (ALK) (pH=7.59 ± 0.01) ALK with iNO(40 ppm). Results: Table below compares changes between PLV and IPPV for each sequence (mean ± s.e.m). The changes in PVR and oxygenation (Aa02: alveolar-arterial 02 gradient) are shown as% change from the previous eucapneic state. Cardiac output (C.O.) is in ml/min/kg and lung compliance (Cdyn) in ml/cm H2O/kg. Conclusions: prior to TX, the perfluorocarbon caused a density associated cardiovascular depression of moderate degree. However this did not prevent iNO and ALK to be at least as efficient as during IPPV. For both modes of ventilation, iNO and ALK had an additive effect. PLV preserved lung compliance more efficiently than IPPV and could therefore be a more effective mode of treatment in pulmonary hypertension associated with lung injury.