Association of day-case rates with post COVID-19 recovery of elective laparoscopic cholecystectomy activity across England.

INTRODUCTION: The aim of this study was to investigate the safety of day-case laparoscopic cholecystectomy, and the association between day-case rates and, post the COVID-19 pandemic, recovery of activity to prepandemic levels for integrated care boards (ICBs) in England. METHODS: This was a retrospective observational study of the Hospital Episodes Statistics (HES) data set. Elective laparoscopic cholecystectomies for the period 1 January 2019 to 31 December 2022 were identified. Activity levels for 2022 were compared with those for the whole of 2019 (baseline). Day-case activity was identified where the length of stay recorded in the HES was zero days. RESULTS: Data were available for 184,252 patients across the 42 ICBs in England, of which 120,408 (65.3%) were day-case procedures. By December 2022, activity levels for the whole of England had returned to 88.2% of prepandemic levels. The South West region stood out as having recovered activity levels to the greatest extent, with activity at 97.3% of prepandemic levels during 2022. The South West also had the highest postpandemic day-case rate at 74.9% of all patients seen as a day-case during 2022; this compares with an England average of 65.3%. At an ICB level, there was a significant correlation between day-case rates and postpandemic activity levels (r = 0.362, p = 0.019). There was no strong or consistent evidence that day-case surgery had poorer patient outcomes than inpatient surgery. CONCLUSIONS: Recovery of elective laparoscopic cholecystectomy activity has been better in South West England than in other regions. Increasing day-case rates may be important if ICBs in other regions are to increase activity levels up to and beyond prepandemic levels.

Factors associated with conversion from day-case to in-patient elective inguinal hernia repair surgery across England: an observational study using administrative data.

PURPOSE: Elective primary inguinal hernia repair surgery is increasingly being conducted as a day-case procedure. However, some patients planned for day-case surgery have to stay in hospital for at least one night. The aim of this study was to identify the factors associated with conversion from day-case to in-patient management for elective inguinal hernia repair surgery. METHODS: This was an exploratory retrospective analysis of observational data from the Hospital Episode Statistics dataset for England. All patients aged ≥ 17 years undergoing a first elective inguinal hernia repair between 1st April 2014 and 31st March 2022 that was planned as day-case surgery were identified. The exposure of interest was discharged on the day of admission (day-case) or requiring overnight stay. The primary outcome of interest was 30-day emergency readmission with an overnight stay. For reporting, providers were aggregated to an Integrated Care Board (ICB) level. RESULTS: A total of 351,528 planned day-case elective primary inguinal hernia repairs were identified over the eight-year study period. Of these, 45,305 (12.9%) stayed in hospital for at least one night and were classed as day-case to in-patient stay conversions. Patients who converted to in-patient stay were older, had more comorbidities, and were more likely to have bilateral surgery and be operated on by a low-annual volume surgeon. Post-procedural complications were strongly associated with conversion. Across the 42 ICBs in England, model-adjusted conversion rates varied from 3.3% to 21.3%. CONCLUSIONS: There was considerable variation in conversion to in-patient stay rates for inguinal hernia repair across ICBs in England. Our findings should help surgical teams to better identify patients suitable for day-case inguinal hernia repair and plan discharge services more effectively. This should help to reduce the variation in conversion rates.

Day-case and in-patient elective inguinal hernia repair surgery across England: an observational study of variation and outcomes.

PURPOSE: Elective primary inguinal hernia repair surgery is increasingly being conducted as a day-case procedure. However, in England there is evidence of wide variation in day-case rates across hospitals. Reducing the extent of this variation has the potential to support more efficient use of resources (e.g., clinician time, hospital beds) and help the recovery of elective surgical activity following the COVID-19 pandemic. The aims of this study were to explore the extent of variation in day-case rates across healthcare providers in England and to evaluate the safety of day-case elective primary inguinal hernia repair surgery. METHODS: This was an exploratory, retrospective analysis of observational data from the Hospital Episode Statistics data set for England. All patients aged ≥ 17 years undergoing a first elective inguinal hernia repair between 1st April 2014 and 31st March 2022 were identified. The exposure of interest was day-case or in-patient stay, and the primary outcome of interest was 30-day emergency readmission with an overnight stay. For reporting, providers were aggregated to an Integrated Care Board (ICB) level. RESULTS: A total of 413,059 elective primary inguinal hernia repairs were identified over the 8-year study period. Of these, 326,833 (79.1%) were day-case procedures. During the most recent financial year (2021-22), the highest day-case rate for an ICB was 93.8% and the lowest 66.1%. After adjusting for covariates, day-case surgery was associated with significantly lower rates of 30-day emergency readmission (odds ratio (OR) 0.61, 95% confidence interval (CI) 0.58-0.64, p < 0.001) and for the secondary outcomes 180-day mortality and haemorrhage, infection and pain at 30-day post-discharge. Rates of 30-day emergency readmission were significantly lower in ICBs with high rates of day-case surgery (OR 0.84, 95% CI 0.74-0.96, p < 0.001) than in ICBs with low rates of day-case surgery, although rates of post-procedural haemorrhage within 30 days of discharge were significantly higher in trusts with high day-case rates (OR 1.20, 95% CI 1.04-1.40, p = 0.015). CONCLUSIONS: For the outcomes studied, we found no consistent evidence that day-case elective inguinal hernia repair was unsafe for selected patients. Currently, there is substantial variation between ICBs in terms of delivering day-case surgery. Reducing this variability may help address the current pressures on the NHS in elective surgery.

Optimization of continuous hydrothermal treatment for improving the dehulling of black gram (Vigna mungo L).

Black gram kernels with three initial moisture contents (10, 14 & 18 % w.b.) were steam treated in a continuous steaming unit at three inlet steam pressures (2, 3 & 4 kg/cm(2)) for three grain residence times (2, 4 & 6 min) in order to determine best treatment condition for maximizing the dhal yield while limiting the colour change in acceptable range. The dhal yield, dehulling loss and the colour difference (Delta E*) of the dehulled dhal were found to vary respectively, from 56.4 to 78.8 %, 30.8 to 8.6 % and 2.1 to 9.5 with increased severity of treatment. Optimization was done in order to obtain higher dhal yield while limiting the colour difference (Delta E*) within acceptable range i.e. 2.0 to 3.5 using response surface methodology. The best condition was obtained with the samples having 13.1 % initial moisture treated with 4 kg/cm(2) for about 6 min to achieve a dhal yield of 71.2 % and dehulling loss of 15.5 %.

Microwave assisted dehulling of black gram (Vigna mungo L).

This article summarises the results of the investigation of application of microwave exposure on the dehulling characteristics of the black gram and the properties of the dehulled grains. Black gram was exposed to 3 microwave power levels, viz., 450, 630 and 810 W for 7 different exposure, ranging from 60 to 150 s at an interval of 15 s with a view to determine the suitable combination of dosage in order to get the maximum yield with little change in colour. Related changes in properties were also studied. It was observed that the surface temperature of the grain increased with the increase in microwave power level from 450 to 810 W as well as exposure time from 60 to 150 s in the range from 58 to 123 °C while the dehulling time reduced from 445 to 170 s. The dehulling yield increased with increasing microwave dosage in the beginning and reached to the maximum value followed by decreasing trend. The colour of the dehulled grain changed slowly up to a microwave dosage of 972 J/g after that it changed vividly darker than the control. The dehulling and dhal yields and colour change were polynomial functions of microwave dosage. The highest yield of 73.7 % was achieved at about 972 J/g with a little change in colour (CIELAB ΔE* value of 2.58). The corresponding dehulling time, cooking time and losses during dehulling were respectively 185 s, 10 min and 15.1 % as compared to 492 s, 20 min and 31.5 % for control respectively. It is concluded that a dosage of about 972 J/g was the best for the black gram dehulling at a rate of 630 W or higher power level.

Target-directed catalytic metallodrugs.

Most drugs function by binding reversibly to specific biological targets, and therapeutic effects generally require saturation of these targets. One means of decreasing required drug concentrations is incorporation of reactive metal centers that elicit irreversible modification of targets. A common approach has been the design of artificial proteases/nucleases containing metal centers capable of hydrolyzing targeted proteins or nucleic acids. However, these hydrolytic catalysts typically provide relatively low rate constants for target inactivation. Recently, various catalysts were synthesized that use oxidative mechanisms to selectively cleave/inactivate therapeutic targets, including HIV RRE RNA or angiotensin converting enzyme (ACE). These oxidative mechanisms, which typically involve reactive oxygen species (ROS), provide access to comparatively high rate constants for target inactivation. Target-binding affinity, co-reactant selectivity, reduction potential, coordination unsaturation, ROS products (metal-associated vs metal-dissociated; hydroxyl vs superoxide), and multiple-turnover redox chemistry were studied for each catalyst, and these parameters were related to the efficiency, selectivity, and mechanism(s) of inactivation/cleavage of the corresponding target for each catalyst. Important factors for future oxidative catalyst development are 1) positioning of catalyst reduction potential and redox reactivity to match the physiological environment of use, 2) maintenance of catalyst stability by use of chelates with either high denticity or other means of stabilization, such as the square planar geometric stabilization of Ni- and Cu-ATCUN complexes, 3) optimal rate of inactivation of targets relative to the rate of generation of diffusible ROS, 4) targeting and linker domains that afford better control of catalyst orientation, and 5) general bio-availability and drug delivery requirements.

Target-directed catalytic metallodrugs

Most drugs function by binding reversibly to specific biological targets, and therapeutic effects generally require saturation of these targets. One means of decreasing required drug concentrations is incorporation of reactive metal centers that elicit irreversible modification of targets. A common approach has been the design of artificial proteases/nucleases containing metal centers capable of hydrolyzing targeted proteins or nucleic acids. However, these hydrolytic catalysts typically provide relatively low rate constants for target inactivation. Recently, various catalysts were synthesized that use oxidative mechanisms to selectively cleave/inactivate therapeutic targets, including HIV RRE RNA or angiotensin converting enzyme (ACE). These oxidative mechanisms, which typically involve reactive oxygen species (ROS), provide access to comparatively high rate constants for target inactivation. Target-binding affinity, co-reactant selectivity, reduction potential, coordination unsaturation, ROS products (metal-associated vs metal-dissociated; hydroxyl vs superoxide), and multiple-turnover redox chemistry were studied for each catalyst, and these parameters were related to the efficiency, selectivity, and mechanism(s) of inactivation/cleavage of the corresponding target for each catalyst. Important factors for future oxidative catalyst development are 1) positioning of catalyst reduction potential and redox reactivity to match the physiological environment of use, 2) maintenance of catalyst stability by use of chelates with either high denticity or other means of stabilization, such as the square planar geometric stabilization of Ni- and Cu-ATCUN complexes, 3) optimal rate of inactivation of targets relative to the rate of generation of diffusible ROS, 4) targeting and linker domains that afford better control of catalyst orientation, and 5) general bio-availability and drug delivery requirements.

Angiotensin-(1-7) serves as an aquaretic by increasing water intake and diuresis in association with downregulation of aquaporin-1 during pregnancy in rats.

We previously demonstrated that kidney and urine levels of angiotensin-(1-7) [ANG-(1-7)] were increased in pregnancy. To explore the role of ANG-(1-7) on fluid and electrolyte homeostasis during pregnancy, we evaluated the effect of the ANG-(1-7) antagonist D-alanine-[ANG-(1-7)] (A-779) on kidney function. Virgin and pregnant rats received infusion of vehicle or A-779 (48 microg.kg(-1).h(-1)) for 8 days by osmotic minipumps. Metabolic studies were done on treatment day 7-8. Virgin and pregnant rats at day 15 and 19 were killed, and blood and kidneys were collected. Kidneys were prepared for Western blot analysis for aquaporin-1 (AQP1) and aquaporin-2. In virgin female rats, A-779 increased urine volume and decreased urinary osmolality and AQP1 with no change in water intake. In 19-day pregnant rats, A-779 significantly decreased water intake and urine volume and increased urinary osmolality and kidney AQP1 expression. Only in late gestation did A-779 treatment decrease the difference between intake and output (balance). A-779 treatment increased plasma vasopressin in late gestation but did not change vasopressin in virgins. In virgin and pregnant animals, A-779 administration had no effect on blood pressure, plasma volume, blood volume, or urinary electrolytes. These results suggest that ANG-(1-7) produces antidiuresis associated with upregulation of AQP1 in virgin rats, whereas ANG-(1-7) produces diuresis in late gestation with downregulation of AQP1. ANG-(1-7) contributes to the enhanced water intake during pregnancy, allowing maintenance of the normal volume-expanded state despite diuresis produced in part by decreased AVP and AQP1.

Administration of D-Alanine-[Ang-(1-7)] (A-779) Prior to Pregnancy in Sprague Dawley Rats Produces Antidiuresis in Late Gestation.

We previously demonstrated that angiotensin-(1-7) [Ang-(1-7)], which is increased in the kidney and urine during pregnancy, influences normal fluid expansion of pregnancy. These previous studies were completed by chronic administration of the Ang-(1-7) receptor antagonist D-Alanine-[Ang-(1-7)] (A-779) at a dose of 48 µg/kg/hr after the start of pregnancy (gestational days 11-19). To further explore the role of Ang-(1-7) on kidney function during early, middle, and late pregnancy, Sprague Dawley rats were chronically pretreated 8 days prior to pregnancy and throughout pregnancy (gestational days 0-19) with vehicle or A-779 at a dose of 24 µg/kg/hr. Metabolic studies were completed in virgin animals and throughout pregnancy (gestational days 4-5, 14-15, and 18-19). Chow consumption and water intake increased throughout pregnancy while the difference between intake and output (balance) was increased only at late (day 19) pregnancy with both vehicle and A-779 administration. Urine volume and urinary osmolality were significantly increased and decreased respectively throughout pregnancy in vehicle treated rats only. In late (19 day) pregnancy, A-779 administration significantly decreased chow consumption and water intake. In virgin animals, A-779 administration significantly increased urine volume, while during late pregnancy (19 day), urine volume was significantly decreased with A-779 administration. These studies using pretreatment with a lower dose of A-779 prior to pregnancy confirm results of higher dose A-779 administration after the start of pregnancy. These studies show that Ang-(1-7) produces antidiuresis in virgin rats and diuresis in late gestation. Ang-(1-7) also contributes to the enhanced water intake during pregnancy allowing maintenance of the normal volume expanded state despite diuresis.

Temporal-spatial expression of ANG-(1-7) and angiotensin-converting enzyme 2 in the kidney of normal and hypertensive pregnant rats.

We recently demonstrated that renin-angiotensin system (RAS) overactivity during late gestation in rats is associated with increased kidney and urine levels of ANG-(1-7) and enhanced kidney immunostaining of ANG-(1-7) and angiotensin-converting enzyme 2 (ACE2). To understand the temporal-spatial changes in normal and hypertensive pregnancies, the renal distribution of ANG-(1-7) and ACE2 in association with kidney angiotensin peptides and ACE2 activity was examined in virgin, normal pregnant (NP; gestational days 5, 15, and 19) and reduced uterine perfusion pressure (RUPP at day 19) pregnant Sprague-Dawley rats. ANG-(1-7) and ACE2 immunocytochemical staining increased 1.8- and 1.9-fold and 1.7- and 1.8-fold, respectively, at days 15 and 19 of NP, compared with virgin rats. ANG-(1-7) and ANG II concentrations were increased in the kidney at 19 days of gestation. ACE2 activity measured using a fluorescent substrate was increased 1.9- and 1.9-fold in the cortex and 1.9- and 1.8-fold in the medulla at days 15 and 19 of NP. In the RUPP animals, ANG-(1-7) immunostaining and concentration were significantly decreased compared with 19-day NP rats. ACE2 activity was unchanged in the cortex and medulla of RUPP rats. In conclusion, during NP, the concurrent changes of ACE2 and ANG-(1-7) suggest that ACE2 plays an important role in regulating the renal levels of ANG-(1-7) at mid to late gestation. However, the decrease in renal ANG-(1-7) content in the absence of a concomitant decrease in ACE2 implicates the participation of other ANG-(1-7) forming or degrading enzymes during hypertensive pregnancy.

Enhanced expression of Ang-(1-7) during pregnancy

Pregnancy is a physiological condition characterized by a progressive increase of the different components of the renin-angiotensin system (RAS). The physiological consequences of the stimulated RAS in normal pregnancy are incompletely understood, and even less understood is the question of how this system may be altered and contribute to the hypertensive disorders of pregnancy. Findings from our group have provided novel insights into how the RAS may contribute to the physiological condition of pregnancy by showing that pregnancy increases the expression of both the vasodilator heptapeptide of the RAS, angiotensin-(1-7) [Ang-(1-7)], and of a newly cloned angiotensin converting enzyme (ACE) homolog, ACE2, that shows high catalytic efficiency for Ang II metabolism to Ang-(1-7). The discovery of ACE2 adds a new dimension to the complexity of the RAS by providing a new arm that may counter-regulate the activity of the vasoconstrictor component, while amplifying the vasodilator component. The studies reviewed in this article demonstrate that Ang-(1-7) increases in plasma and urine of normal pregnant women. In preeclamptic subjects we showed that plasma Ang-(1-7) was suppressed as compared to the levels found in normal pregnancy. In addition, kidney and urinary levels of Ang-(1-7) were increased in pregnant rats coinciding with the enhanced detection and expression of ACE2. These findings support the concept that in normal pregnancy enhanced ACE2 may counteract the elevation in tissue and circulating Ang II by increasing the rate of conversion to Ang-(1-7). These findings provide a basis for the physiological role of Ang-(1-7) and ACE2 during pregnancy.

Enhanced expression of Ang-(1-7) during pregnancy.

Pregnancy is a physiological condition characterized by a progressive increase of the different components of the renin-angiotensin system (RAS). The physiological consequences of the stimulated RAS in normal pregnancy are incompletely understood, and even less understood is the question of how this system may be altered and contribute to the hypertensive disorders of pregnancy. Findings from our group have provided novel insights into how the RAS may contribute to the physiological condition of pregnancy by showing that pregnancy increases the expression of both the vasodilator heptapeptide of the RAS, angiotensin-(1-7) [Ang-(1-7)], and of a newly cloned angiotensin converting enzyme (ACE) homolog, ACE2, that shows high catalytic efficiency for Ang II metabolism to Ang-(1-7). The discovery of ACE2 adds a new dimension to the complexity of the RAS by providing a new arm that may counter-regulate the activity of the vasoconstrictor component, while amplifying the vasodilator component. The studies reviewed in this article demonstrate that Ang-(1-7) increases in plasma and urine of normal pregnant women. In preeclamptic subjects we showed that plasma Ang-(1-7) was suppressed as compared to the levels found in normal pregnancy. In addition, kidney and urinary levels of Ang-(1-7) were increased in pregnant rats coinciding with the enhanced detection and expression of ACE2. These findings support the concept that in normal pregnancy enhanced ACE2 may counteract the elevation in tissue and circulating Ang II by increasing the rate of conversion to Ang-(1-7). These findings provide a basis for the physiological role of Ang-(1-7) and ACE2 during pregnancy.

Effects of rosiglitazone and linoleic acid on human preadipocyte differentiation.

BACKGROUND: Peroxisome proliferator activated receptor gamma (PPARgamma) is a ligand-activated transcription factor known to be central to both adipose tissue development and insulin action. Growth of adipose tissue requires differentiation of preadipocytes with acquisition of specific cellular functions including insulin sensitivity, leptin secretion and the capacity to store triglyceride. Dietary fatty acids and members of the thiazolidinedione class of compounds have been reported to influence adipogenesis at the transcriptional level. Here, we compare the effects of a dietary fatty acid, linoleic acid, and a thiazolidinedione, rosiglitazone, on biochemical and functional aspects of human preadipocyte differentiation in vitro. MATERIALS AND METHODS: Human omental and subcutaneous preadipocytes were subcultured 2-3 times and subsequently differentiated for 21 days in the presence of either linoleic acid or rosiglitazone. Differentiation was assessed using a number of biochemical and functional parameters. RESULTS: Omental and subcutaneous preadipocytes differentiated in the presence of linoleic acid showed marked cytoplasmic triacylglycerol accumulation however, no biochemical markers of differentiation (LPL expression, G3PDH gene expression and enzyme activity and leptin expression or secretion) were detected. In contrast, treatment of these cells with rosiglitazone induced full biochemical differentiation as judged by all markers assessed, despite comparatively little lipid accumulation. The rosiglitazone effects were subcutaneous depot-specific. Cells treated with linoleic acid showed decreased glucose uptake cf rosiglitazone-treated cells. A luciferase reporter assay demonstrated that rosiglitazone potently activates h-peroxisome proliferator activated receptor gamma while linoleic acid had no effect. CONCLUSIONS: These studies demonstrate that (a) human preadipocytes have the potential to accumulate triacylglycerol irrespective of their stage of biochemical differentiation; (b) while omental preadipocytes are refractory to biochemical differentiation in vitro, they are able to accumulate triacylglycerol; and (c) rosiglitazone and linoleic acid may exert their effects via different biochemical pathways.

Greater replication and differentiation of preadipocytes in inherited corticosteroid-binding globulin deficiency.

Glucocorticoids are pivotal for adipose tissue development. Rodent studies suggest that corticosteroid-binding globulin (CBG) modulates glucocorticoid action in adipose tissue. In humans, both genetic CBG deficiency and suppressed CBG concentrations in hyperinsulinemic states are associated with obesity. We hypothesized that CBG deficiency in humans modulates the response of human preadipocytes to glucocorticoids, predisposing them to obesity. We compared normal preadipocytes with subcultured preadipocytes from an individual with the first ever described complete deficiency of CBG due to a homozygous null mutation. CBG-negative preadipocytes proliferated more rapidly and showed greater peroxisome proliferator-activated receptor-gamma-mediated differentiation than normal preadipocytes. CBG was not expressed in normal human preadipocytes. Glucocorticoid receptor number and binding characteristics and 11beta-hydroxysteroid dehydrogenase activity were similar for CBG-negative and normal preadipocytes. We propose that the increased proliferation and enhanced differentiation of CBG-negative preadipocytes may promote adipose tissue deposition and explain the obesity seen in individuals with genetic CBG deficiency. Furthermore, these observations may be relevant to obesity occurring with suppressed CBG concentrations associated with hyperinsulinemia.

Intrinsic regional differences in androgen receptors and dihydrotestosterone metabolism in human preadipocytes.

Androgens play an important role in regulating the central obesity that is a strong risk factor for cardiovascular disease and insulin resistance. This study confirms that androgen receptors are present in subcultured human preadipocytes, with androgen receptor gene expression and saturable specific dihydrotestosterone binding, dissociation constant 1.02 - 2.56 nM and maximal binding capacity 30.8 - 55.7 fmol/mg protein. There was an intrinsic regional difference in androgen receptor complement, with more androgen receptors in visceral than in subcutaneous preadipocytes. Dihydrotestosterone was metabolised by human preadipocytes, with more androstanediol produced by subcutaneous than visceral preadipocytes. While dihydrotestosterone metabolism was insufficient to explain the regional variation in androgen binding, both of these differences would reduce the androgen responsiveness of the subcutaneous preadipocytes compared with visceral preadipocytes. There were no gender differences in androgen binding or metabolism. While the direct effects of androgens on human PAs remain uncertain, these regional differences suggest that AR-mediated regulation of certain PA functions influences adipose tissue distribution.

Estrogen receptors in human preadipocytes.

Estrogen influences regional adipose tissue distribution and the accompanying cardiovascular disease risk. To elucidate the mechanisms of this link further, we assessed whether human preadipocytes (PAs) expressed estrogen receptors (ERs) and whether there were any regional or gender differences in ER complement. Human PAs expressed the ERalpha gene but not ERbeta by reverse transcriptase-polymerase chain reaction, possessed ERa protein on Western blotting, and displayed specific 17beta-estradiol (E2) binding with calculated dissociation constants of 0.78 nM, 0.96 nM, and 1.19 nM and maximal binding capacities of 9.3 fmol/mg, 14.6 fmol/ mg, and 18.2 fmol/mg from three whole cell binding assays. There were no regional differences in ERalpha complement for males or females. There were no gender differences in ERalpha complement for subcutaneous or visceral samples. We conclude that ERa but not ERbeta is present in human PAs. This suggests that the effect of estrogen on adipose tissue deposition has a contribution from the direct effect of estrogen on human PAs via ERa.

New retirement plan designs based on new laws and regulations.

Retirement plan design laws have recently undergone changes that could provide significant benefits to physicians. The issues are complex, however. Effective retirement plan strategies for physicians must be crafted to align with specific goals; no clear "best choice" plan exists. This article outlines the intricacies of various funding options for retirement benefits for physicians and medical office staff. Several examples illustrate several of the permutations that are available to achieve a variety of goals. Physicians seeking to maximize benefits while minimizing economic impact should seek counsel from a competent expert on retirement plan design.

Effects of group B streptococci on cord and adult mononuclear cell interleukin-12 and interferon-gamma mRNA accumulation and protein secretion.

Group B streptococci (GBS) are a major cause of early-onset infection in neonates. Neonates, who have defects in neutrophil function that likely contribute to susceptibility to GBS infection, are deficient in the production of the phagocyte activator interferon (IFN)-gamma. GBS-stimulated mRNA accumulation and protein secretion of IFN-gamma and interleukin (IL)-12, a major enhancer of IFN-gamma production, by mixed mononuclear cells (MMCs) from umbilical cord and adult peripheral blood was examined. GBS-exposed cord blood MMCs secreted lower concentrations of both IL-12 and IFN-gamma proteins than did MMCs from adults. IL-12 and IFN-gamma mRNA accumulation was examined by use of comparative reverse transcriptase-polymerase chain reaction. Cord blood MMCs accumulated less mRNA for both IL-12 and IFN-gamma than did adult blood MMC. The deficiency in cord blood cell production of IL-12 may have a role in inadequate IFN-gamma production, which contributes to the unique susceptibility of neonates to GBS infections.

Glucocorticoid receptors in human preadipocytes: regional and gender differences.

Glucocorticoid excess causes visceral obesity and its accompanying insulin resistance, dyslipidemia and hypertension. Glucocorticoids enhance preadipocyte (PA) differentiation and increase their aromatase activity (oestrogen production) and there is regional variability in these PA processes. Therefore, we studied human PAs for the presence of, and any regional or gender differences in, glucocorticoid receptors (GRs). Confluent subcultured human subcutaneous (Sc) and visceral (Vis) PAs from both genders contained GRs as assessed by GR gene expression and specific glucocorticoid (dexamethasone) binding. The dissociation constant was similar to that of other human cells and there was no difference between Sc and Vis sites or between males and females. There was significantly less GR mRNA in Vis PAs compared with Sc PAs in females (P=0.008) but not in males. There was less glucocorticoid binding in Vis compared with Sc PAs in females, measured by maximal binding capacity (P=0.035) or single saturating dose glucocorticoid binding (Bssd) (P=0.019). There was no regional difference in specific glucocorticoid binding in males. There was a gender difference with fewer GRs in Vis PAs in females compared with males measured by Bssd (P=0.006). In summary, GRs are present in human PAs. There is a lower GR density in Vis compared with Sc PAs in females, and females have fewer GRs in Vis PAs compared with males. These differences are likely to affect regional aromatase activity and to contribute to the smaller visceral fat mass in females compared with males.