High-intensity interval training improves insulin sensitivity in older individuals.

AIM: Metabolic health may deteriorate with age as a result of altered body composition and decreased physical activity. Endurance exercise is known to counter these changes delaying or even preventing onset of metabolic diseases. High-intensity interval training (HIIT) is a time efficient alternative to regular endurance exercise, and the aim of this study was to investigate the metabolic benefit of HIIT in older subjects. METHODS: Twenty-two sedentary male (n = 11) and female (n = 11) subjects aged 63 ± 1 years performed HIIT training three times/week for 6 weeks on a bicycle ergometer. Each HIIT session consisted of five 1-minute intervals interspersed with 1½-minute rest. Prior to the first and after the last HIIT session whole-body insulin sensitivity, measured by a hyperinsulinaemic-euglycaemic clamp, plasma lipid levels, HbA1c, glycaemic parameters, body composition and maximal oxygen uptake were assessed. Muscle biopsies were obtained wherefrom content of glycogen and proteins involved in muscle glucose handling were determined. RESULTS: Insulin sensitivity (P = .011) and maximal oxygen uptake increased (P < .05) in both genders, while plasma cholesterol (P < .05), low-density lipoprotein (P < .05), visceral fat mass (P < .05) and per cent body fat (P < .05) decreased after 6 weeks of HIIT. HbA1c decreased only in males (P = .001). Muscle glycogen content increased in both genders (P = .001) and in line GLUT4 (P < .05), glycogen synthase (P = .001) and hexokinase II (P < .05) content all increased. CONCLUSION: Six weeks of HIIT significantly improves metabolic health in older males and females by reducing age-related risk factors for cardiometabolic disease.

Surface charge, fluidity, and calcium uptake by rat intestinal brush-border vesicles.

Biological membrane outer surfaces are negatively charged and interact with positively charged calcium ion during calcium uptake. Positively charged polycations such as polyarginine bind to membranes with high affinity, displacing bound calcium from the membrane. We tested the effect of polyarginine on uptake of calcium by brush-border membrane vesicles and examined the responses in terms of membrane fluidity by electron paramagnetic resonance (EPR). Polyarginine inhibited the saturable component of calcium uptake by a mechanism combining inhibition characteristics of strontium (competitive) and magnesium (non-competitive). Unlike the inhibition of non-saturable calcium uptake by strontium and magnesium, polyarginine increased kD, the rate constant for non-saturable calcium uptake, by a concentration dependent mechanism. These effects of polyarginine on calcium uptake were associated with decreased membrane fluidity at the uptake temperature. These findings are consistent with a role for surface negative charge in determining both saturable and non-saturable calcium uptake. Increased membrane fluidity is associated with decreased saturable and increased non-saturable calcium uptake. Although increased fluidity might be involved in the increased kD for non-saturable uptake, the concentration-specific stimulating effect of polyarginine suggests a gating mechanism.

Brush border calcium uptake in short-bowel syndrome in rats.

Resection of distal small intestine causes calcium malabsorption in humans and in a rat model of 50% distal resection. We tested the hypothesis that this calcium malabsorption is caused in the rat model by a brush border defect. We compared brush border membrane vesicles from the proximal small intestine of control (transection and anastomosis at mid-small intestine) with distally resected rats. Mucosal protein was 25% greater in the resected group and the vesicles were enriched 37-fold in sucrase activity when compared with homogenate. Kinetic constants Vmax (maximal initial rate of saturable calcium uptake at infinite concentration), kT (calcium concentration for saturable calcium uptake rate at half Vmax), and KD (rate constant for nonsaturable calcium uptake per unit concentration) were slightly but not significantly greater in the resected as compared with the transected group, ruling out the brush border as the cause for decreased transmucosal calcium transport.

Vitamin D and enterocyte brush border membrane calcium transport and fluidity in the rat.

Prior studies of vitamin D repletion showed a threefold increase in the maximum rate (Vmax) for calcium uptake by brush border membrane vesicles, but did not differentiate saturable and nonsaturable uptake components. We studied the calcium uptake and fluidity response of intestinal brush border vesicles to vitamin D by treatment with 1 alpha,25-dihydroxy-24,24-difluorocholecalciferol (24,24-F-1,25-(OH)2D3). Treatment responses were measured by effects on (1) saturable and nonsaturable initial uptake rates of calcium by rat proximal small intestinal brush border membrane vesicles; (2) transmucosal calcium transport by everted duodenal sac; and (3) fluorescence anisotropy. Treatment of vitamin D-depleted weanlings increased the Vmax by 50% (P < .05) in vesicles from the proximal 12 cm of small intestine from rats injected with disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP), but there was no response in rats not injected with EHDP or in vesicles from the proximal 30 cm of small intestine. Vitamin D-depleted weanlings were D-deficient based on serum 25-hydroxycalciferol(25-OH-D) concentration, but to produce 1 alpha,25-dihydroxycalciferol [1,25-(OH)2D] depletion, EHDP injection was required. Treatment of vitamin D-replete adult rats caused a 20% (P < .05) increase in Vmax. Treatment did not affect the calcium concentration at half-Vmax (KT), the rate constant for nonsaturable uptake (KD), or vesicle fluidity measured as fluorescence anisotropy. Contrasting with these minimal effects of treatment on brush border Vmax, treatment increased transmucosal calcium transport by everted duodenal sac almost threefold in vitamin D-depleted weanlings administered EHDP. Thus, vitamin D actions on enterocyte calcium transport (1) at the brush border increase saturable but not nonsaturable uptake, and (2) produce the major transport response distal to the brush border. Despite previously described changes in membrane lipid, brush border fluidity is unaffected by vitamin D treatment.

Infection as a predominant cause of perinatal mortality.

During a 15-month period, all 34 infants delivered at the department of obstetrics and gynecology at University Hospital in Lund, Sweden, who died perinatally or neonatally were included in a prospective study of causes of death. Autopsies--including extensive culturing of specimens for bacteria, chlamydia, fungi, mycoplasmas, and viruses--were performed for all infants. Maternal sera obtained during pregnancy and after delivery were examined regarding titers against a number of microorganisms. During the study period, the perinatal mortality rate was 0.60% and the neonatal mortality rate 0.56%. It was found that 37% of the deaths were caused by lethal malformations, 17% by idiopathic respiratory distress syndrome, and 9% by ablatio placentae. However, no less than 21% occurred as a direct consequence of infections, including 2 deaths caused by group B streptococci, 2 by Coxsackie B virus, and 3 deaths each by Hemophilus influenzae, Pseudomonas pyocyanea, and Candida albicans. A 6-month study of late abortions revealed another case of intrauterine group B streptococcal infection. The study has demonstrated that autopsy, including microbial examination, is recommended in all cases of perinatal and neonatal deaths.

Chronic carrier state in mothers of infants with group B streptococcal infections.

Seven of eight women who had given birth to infants with early onset or intrauterine infection caused by group B streptococci remained carriers of the same serotype of group B streptococci up to 38 months after their pregnancy. In contrast, only 34 of 88 group B streptococci carriers who had given birth to healthy infants harbored the same serotype at the 34 months' follow-up (P = .009). Among the control subjects, 29 of 71 showed increased serum levels at followup of antibodies against the serotype isolated at delivery, a significantly higher proportion compared with the mothers of infected infants/fetuses. The results indicate that mothers of group B streptococci-infected infants are chronic urogenital carriers of group B streptococci without responding immunologically against the organism.

Risk factors in cesarean section infection.

Factors associated with risk of postoperative infection after cesarean section were studied in 321 patients not given antibiotic prophylaxis. Infections occurred in 56 (25%) of the 228 patients who were delivered by emergency cesarean section and in eight (9%) of the 93 patients who underwent elective surgery (P less than .01). These frequencies corresponded well with the infection rates reported after administration of antibiotics in other studies. Risk factors were: duration of operation more than one hour; blood loss more than 800 ml; presence of Staphylococcus aureus in the nares; signs of intrauterine infection before surgery; and failure of progress in labor. The results indicated that obstetric interventions had been performed more frequently in patients at risk of infection, rather than being the real cause of the infections. The importance of strict preoperative hygienic routine is discussed.

Effect of ritodrine on labor after premature rupture of the membranes.

The effect on labor of administering ritodrine after a premature rupture of the membranes (PROM) was studied in a double-blind trial in 30 patients. The patients were selected according to the following criteria: 28 to 36 weeks' gestation, only 1 fetus, cervix dilated 4 cm or less, and absence of pyrexia or other signs of uterine infection. Fourteen patients received ritodrine and 16 received a placebo. The 2 groups were statistically comparable. None of the patients receiving ritodrine delivered within 24 hours. The difference between the 2 groups was statistically significant with respect to the number of patients delivered within 24 hours (P less than 0.05). However, after 24 hours, there was no difference between the groups as regards the length of pregnancy. The infections registered in the mothers of infants were few and easily controlled. The incidence of idiopathic respiratory distress syndrome (IRDS) was low in the study and allows no conclusions concerning the benefit of prolonging the pregnancy for more than 24 hours after PROM.

A study of complications in preterm deliveries after prolonged premature rupture of the membranes.

The risk of infection for mother and baby after spontaneous rupture of the membranes was evaluated in a prospective study of 24 patients with ruptured membranes before the 36th week of pregnancy. The mean length of pregnancy after rupture was 10 days and 2 hours. Only patients harboring Group B streptococci or E. coli in the urogenital tract were treated with antibiotics (during delivery). With the exception of 1 woman, all patients harbored one or more pathogens in the urogenital tract. Four mothers were infected but all recovered. One of 26 infants died from infection. The study did not confirm any association between prolonged rupture of the membranes and the frequency of idiopathic respiratory distress syndrome, nor did it contradict attempts to actively prolong pregnancy after rupture of the membranes.

Colonisation of the upper respiratory tract of mice with group B streptococci type III with reference to the R-protein.

Nine strains of group B streptococci type III, five with R-protein (R+) and four without (R-) were tested for capacity to colonise the upper respiratory tract in mice and to adhere to human buccal cells. In the mouse model, 80-microliter inocula of dilutions of overnight cultures of the strains in Todd Hewitt broth were placed in the external nares under light ether anaesthesia. A pilot experiment demonstrated that it was reasonable to study the throat colonisation 2 and 4 days after inoculation. Groups of 18-20 mice were then given inocula containing 8 X 10(6) cfu/ml of five R+ and four R- strains. At day 4, significantly more mice were colonised with type III, R+ strains (73% of the animals) than with type III, R- strains (44%) (p less than 0.01). In adherence experiments with human buccal cells, no difference was found between the R+ and R- strains. The results indicated that the higher colonisation rate among R+ strains was mediated by mechanisms other than adherence.

Early-onset neonatal group B streptococcal septicaemia in siblings.

At each of two consecutive deliveries, a woman gave birth to a baby that developed early-onset group B streptococcal (GBS) septicaemia. A low titre of serum antibodies to the type of the infecting GBS and persistence of the organism in the mother were demonstrated. This case confirms that mothers of GBS infected infants are at high risk of their future babies being similarly infected.

Chlorhexidine for prevention of neonatal colonization with group B streptococci. IV. Depressed puerperal carriage following vaginal washing with chlorhexidine during labour.

The effect of vaginal washing with chlorhexidine acetate, 2 g/l at delivery, on the colonization of the urogenital tract with group B streptococci (GBS) 4 days later was investigated. Patients who were culture-positive for GBS in urethra and/or cervix in pregnancy weeks 32 and 36 as well as at delivery were included in a prospective study. The washing procedure was performed in 31 parturients, and 10 (32%) were culture-negative at day 4 after delivery. In contrast, only 7/47 (15%) non-washed controls were negative at day 4 (p = 0.044). The results demonstrate a prolonged suppressive effect of vaginal washing with chlorhexidine on the recovery of GBS from the urogenital tract in this highly selected patient group.

Effect of a strict preoperative hygienic routine on the rate of infections following cesarean section.

The frequency of postoperative infections after cesarean section was studied during two periods. In the first period no strict preoperative hygienic routines were applied; 321 patients were delivered by cesarean section during this period. In the next period strict hygienic routines were introduced; this period included 337 patients. The infection rate was significantly reduced during the second period from 20% to 16%. This reduction was found among the elective operations, and among parturients who had been treated in the hospital for more than 24 h prior to delivery. The frequency of endometritis decreased significantly from the first to the second period, whereas no difference was found concerning wound infections. Significantly fewer patients contracted septicemia during the second period. Since all septicemia cases occurred in endometritis patients the results might indicate that not only the number of patients contracting infection but also the severity of the infections was reduced. No reduction of infections was found after emergency operations. Antibiotic prophylaxis might therefore be of value in this group of patients.

Obstetrical care in future pregnancies after fetal loss in group B streptococcal septicemia. A prevention program based on bacteriological and immunological follow-up.

Among 22 mothers of infants infected with group B streptococci (GBS), 19 showed markedly low levels of antibodies against the infecting type. Three of the patients with low antibody levels went through a new pregnancy within 1 yr after they had lost an infant (2 patients) or experienced fetal death due to GBS (1 patient). They were still urogenital carriers of the type of GBS causing the previous infection, and their serum levels of type-specific antibodies remained low. All three went through a successful pregnancy following a prevention program comprising antibiotic treatment from the 28th wk of pregnancy.

Chlorhexidine for prevention of neonatal colonization with group B streptococci. III. Effect of vaginal washing with chlorhexidine before rupture of the membranes.

A single vaginal washing with 2 g/l of chlorhexidine was performed before rupture of the membranes in 19 parturients who were urogenital carriers of group B streptococci (GBS). Two (11%) of the infants became colonized immediately after birth, in contrast to 16 of 41 (39%) infants to controls (P = 0.02). A significant reduction of GBS colonization of the ear (P = 0.02) and umbilicus (P = 0.01) was noted. Taken together, 2 of 57 (4%) cultures obtained at birth were positive in the chlorhexidine group, in contrast to 30 of 123 (24%) among the controls (P less than 0.01). These findings raise hope for the design of a simple washing procedure which might prevent serious infections in the early neonatal period with GBS but also with other chlorhexidine-sensitive organisms.

Chlorhexidine for prevention of neonatal colonization with group B streptococci. II. Chlorhexidine concentrations and recovery of group B streptococci following vaginal washing in pregnant women.

The effect of a single washing of the urogenital tract with 0.5 g/l chlorhexidine was studied in 6 women in weeks 38-40 of pregnancy, among whom 5 were carriers of group B streptococci in urethra and/or cervix. The chlorhexidine concentrations varied between 25 and 200 mg/l during the first hour after washing in 5 of the 6 women, whereas one patient showed concentrations below 25 mg/l. With the exception of one patient, all individuals showed concentrations less than 25 mg/l at 3-24 h after washing. A clear suppression of the number of colony-forming units of GBS was already apparent after 60 min and was still evident 6 h after chlorhexidine washing.

Chlorhexidine for prevention of neonatal colonization with group B streptococci. V. Chlorhexidine concentrations in blood following vaginal washing during delivery.

Chlorhexidine 2 g/l was applied to the vagina of 96 women during delivery, whereas 28 served as controls. Both groups were given a shower using a chlorhexidine soap, and outer washing of the outer anogenital tract was also performed in all patients using chlorhexidine 2 g/l. Using a gas chromatographic method with a detection limit of 10 ng chlorhexidine per ml blood, 10-83 ng/ml was demonstrated in 34 (35%) of the study group patients, whereas the remaining study group patients and controls showed no detectable chlorhexidine. Performing the washing a second time after 6 hours in 14 patients and a third time in 3 patients after a further 6 hours did not result in increased serum levels. It was concluded that small amounts of chlorhexidine are absorbed through the vaginal mucosa and that chlorhexidine is not accumulated in the blood on repeated usage with 6 hour intervals during delivery.

Chlorhexidine for prevention of neonatal colonization with group B streptococci. I. In vitro effect of chlorhexidine on group B streptococci.

Forty-three strains of group B streptococci (GBS) of types Ia, Ib, II and III were tested for susceptibility to chlorhexidine in concentrations ranging from 256 to 0.25 mg/l using the agar and tube dilution methods. The strains showed minimum inhibitory concentration (MIC) values ranging from 0.5 to 1 mg/l. Serum added to the test medium (50%) increased the MIC values to 4-8 mg/l, while amniotic fluid (50%) had almost no effect, increasing the values to 1-2 mg/l. The minimum bactericidal concentration (MBC) ranged from 1 to 5 mg/l. The killing kinetics were related to the concentration of chlorhexidine and the length of exposure. For example, at a concentration of 63 mg/l, 7 h were required for a bactericidal effect in broth, as compared to 1 h at 500 mg/l chlorhexidine. 200 mg/l chlordexidine had no effect on the adherence of two GBS strains to vaginal epithelial cells, and no effect on the phagocytosis of GBS with mouse peritoneal macrophages.

Transient increase of early-onset group B streptococcal septicemia.

Since 1976, all cases of neonatal group B streptococcal (GBS) septicemia/meningitis have been registered at two Swedish University Hospitals. A significant increase in the number of infants contracting early-onset GBS-septicemia was noticed at one clinic in 1981, from 1-3 cases per yr to 8 cases. Six months prior to this increase the number of deliveries increased from about 1500 per yr to nearly 3000 per yr. It is suggested that external factors, e.g., subtle changes in the nursing combined with an extended disadvantage at the ward might influence the development of early-onset GBS septicemia.