Increased nitric oxide production following chronic hypoxia contributes to attenuated systemic vasoconstriction

Attenuated vasoconstrictor reactivity following chronic hypoxia (CH) is associated with endothelium-dependent vascular smooth muscle (VSM) cell hyperpolarization and diminished intracellular [Ca(2+)]. We tested the hypothesis that increased production of nitric oxide (NO) after CH contributes to blunted vasoconstrictor responsiveness. We found that basal NO production of mesenteric arteries from CH rats (barometric pressure = 380 Torr; 48 h) was greater than that of controls (barometric pressure = 630 Torr). In addition, studies employing pressurized mesenteric arteries (100-200 microM ID) abluminally loaded with the Ca(2+) indicator fura 2-AM demonstrated that although NO synthase (NOS) inhibition normalized agonist-induced vasoconstrictor responses between groups, VSM cell [Ca(2+)] in vessels from CH rats remained diminished compared with controls. To determine whether elevated NO production following CH results from increased NOS protein levels, we performed Western blots for NOS isoforms by using mesenteric arteries from control and CH rats. Endothelial NOS levels did not differ between groups, and other NOS isoforms were not detected in these samples. Selective endothelial loading of fura 2-AM was employed to test the hypothesis that elevated endothelial cell [Ca(2+)] following CH accounts for enhanced NOS activity. These experiments demonstrated greater endothelial cell [Ca(2+)] in mesenteric arteries isolated from CH rats compared with controls. We conclude that enhanced production of NO resulting from elevated endothelial cell [Ca(2+)] contributes to attenuated reactivity following CH by decreasing VSM cell Ca(2+) sensitivity.     

Increased amphetamine potency following chronic naltrexone administration in rats

Chronic administration of the long acting opiate antagonist naltrexone potentiated the amphetamine and apomorphine- -induced stimulation of locomotor activity in rats. Similar treatment also resulted in increased locomotor activity in saline injected rats. The results suggest that chronic opiate receptor blockade may lead to the development of supersensitivity in dopamine systems that mediate motor control. The results provide further support for the notion that endogenous opioids modulate the function of dopamine systems in the brain.     

Increased production of folate by metabolic engineering of Lactococcus lactis

The dairy starter bacterium Lactococcus lactis is able to synthesize folate and accumulates large amounts of folate, predominantly in the polyglutamyl form. Only small amounts of the produced folate are released in the extracellular medium. Five genes involved in folate biosynthesis were identified in a folate gene cluster in L. lactis MG1363: folA, folB, folKE, folP, and folC. The gene folKE encodes the biprotein 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase and GTP cyclohydrolase I. The overexpression of folKE in L. lactis was found to increase the extracellular folate production almost 10-fold, while the total folate production increased almost 3-fold. The controlled combined overexpression of folKE and folC, encoding polyglutamyl folate synthetase, increased the retention of folate in the cell. The cloning and overexpression of folA, encoding dihydrofolate reductase, decreased the folate production twofold, suggesting a feedback inhibition of reduced folates on folate biosynthesis.     

Increased ethanol production by metabolic modulation of cellulose fermentation in Clostridium thermocellum

Significant quantitative differences in ethanol yields along with repression in acetic acid production were observed in Clostridium thermocellum strains SS21 and SS22 in the presence of H 2 , acetone and sodium azide. Exogenous H 2 addition (1.0 atm) increased the ethanol yields to 0.40 g/g and ethanol to acetate ratio to 5.75 in strain SS21 but was inhibitory in strain SS22. Addition of acetone reversed the inhibition caused by H 2 and increased the ethanol yields and ethanol to acetate ratio of strain SS22 up to 0.40 g/g and 7.9, respectively. Enhancement in ethanol yields up to 0.40 g/g and 0.41 g/g and ethanol to acetate ratio up to 3.63 and 8.1 were observed in the presence of 0.2 mM and 0.15 mM concentration of sodium azide by strains SS21 and SS22, respectively.     

Increased endothelin-1 production in patients with chronic heart failure

Endothelin-1 (ET-1) concentrations are elevated in patients with congestive heart failure (CHF), although the cause of this increase remains uncertain. We hypothesized that abnormalities in ET-1 production, clearance, or a combination of these may be the cause of elevated ET-1 concentrations in chronic CHF. The kinetics of clearance of ET-1 were measured with (125)I-labeled ET-1 in eight patients with CHF and five age-matched normal individuals. In both normal subjects and the CHF group, the kinetics of ET-1 clearance were best described by a three-compartment model. The steady-state volume of distribution of ET-1 was significantly greater in the CHF group compared with normal subjects (25.2 +/- 3.9 vs. 13.8 +/- 2.1 l/kg; P < 0.05). The total clearance rate from plasma was greater in the CHF group (0.119 +/- 0.018 vs. 0.047 +/- 0.013 l.kg(-1).min(-1); P = 0.05). The total body production rate of ET-1 was also significantly higher in patients with CHF (0.21 +/- 0.03. vs. 0.06 +/- 0.02 ng.kg(-1).min(-1); P < 0.05). It appears that increased ET-1 production rather than decreased clearance is the cause of elevated ET-1 concentrations in patients with chronic CHF.     

Increased methane production in biogas

Summary Different plant wastes containing digestible volatile solids were tested in admixture with gobar (dung) for their effect in increasing methane output in anaerobic digestion. A mixture of gobar, algae and waterhyacinth in 1 : 1 : 1 proportion produced 79% methane. Parameter affecting the biogas production kinetics are described.     

黑腹绒鼠的代谢产热特征及其体温调节

为探讨东洋界华中区黑腹绒鼠的代谢产热特征及体温调节,本文采用封闭式流体压力呼吸仪对其代谢率、热传导和体温等热生物学指标进行了测定.结果显示:在环境温度为5～25℃的范围内,黑腹绒鼠的体温基本维持恒定,平均体温为36.5±0.1℃;热中性区为25～30℃;基础代谢率为2.99±0.09 ml O2/(g·h);环境温度(Ta)在5～25℃范围内,代谢率(MR)与Ta呈负相关,回归方程为:MR[ ml O2/(g·h)]= 6.56-0.16 Ta(℃),在此范围内,黑腹绒鼠的热传导率C最低,平均为0.26±0.01 ml O2/(g·h·℃).黑腹绒鼠的基本热生物学特征为:较高的BMR、热传导率和体温以及较宽的热中性区.     

Increased heat production proportional to oxygen consumption in human neutrophils activated with phorbol-12-myristate-13-acetate

The heat produced by neutrophils was measured with a flow microcalorimeter. 02 consumption, ATP concentration, lactic acid production and 14CO2 production from oxidation of [1-(14)C]-glucose [6-(14)C]-glucose and [U-14C]-glucose were evaluated. Experiments were also carried out in the presence of the metabolic inhibitors, N-ethylmaleimide and NaF. Heat effects were correlated to the enthalpy change of aerobic and anaerobic glucose catabolism. Two different heat contributions related to two different nonmitochondrial 02 reduction pathways are present during the metabolic burst. Theoretical and experimental data indicate that the reducing power is derived from the catabolism of glucose both through the hexose monophosphate shunt and glycolysis.     

Increased prothrombin time and metabolic changes with high serum aluminum levels following long-term exposure to Bayer-process alumina

Serum aluminum levels twice to three times those in controls were found in 30 of 36 workers in a factory in an atmosphere of alumina dust. Inorganic phosphate and total alkaline phosphatase levels were within normal range, with no clinical evidence of phosphate depletion syndrome. Serum intestinal alkaline phosphatase, acid phosphatase and adenosine triphosphate levels were significantly reduced in the group with high levels of aluminum. The finding that the mean prothrombin time was significantly prolonged is of particular interest with respect to beneficial antithrombogenic effect.     

Changes in vaginal microbiocenosis in patients with chronic pelvic inflammatory diseases following antibiotic therapy

The species composition of the vaginal microorganisms in healthy women and in patients with chronic pelvic inflammatory diseases before and after treatment in a gynecological hospital was studied. The study revealed that antibiotic therapy did not lead to complete clinical convalescence. During bacteriological investigation of patients changes in vaginal microbiocenosis, manifested by a decreased number of microbial species, an increased proportion of Escherichia coli, the occurrence of Staphylococcus aureus, a decreased number of Lactobacillus ssp., were observed. Antibiotic therapy aggravated the dysbiotic microbial picture of the vagina.     

Increased spinal expression of c-Fos following stimulation of the lower urinary tract in chronic spinal cord-injured rats

c-Fos expression was studied in the lumbar and sacral spinal cord regions involved in processing afferent input from the lower urinary tract and a comparison was made between spinal cord-injured (SCI) animals and control animals with intact neuraxes. Afferent pathways from the lower urinary tract were activated either by insertion of a catheter through the urethra into the urinary bladder or by catheterisation plus induction of reflex micturition contractions by intravesical saline infusion. Placement of a catheter alone elicited Fos expression in a similar number of neurones in SCI and control rats mainly in the medial dorsal horn (MDH) and dorsal commissure (DCM) in the segments L1–2 and L5–S1 with a maximum in L5. Additional saline infusion induced low-frequency, high-amplitude, rhythmic bladder contractions of long duration in the rats with intact spinal cords, whereas in SCI rats, bladder distension elicited reflex contractions at a higher frequency, smaller amplitude and shorter duration. However, the basal and mean bladder pressure, as well as the total contraction time relative to the whole recording time, was not significantly different. Distension-induced bladder contractions markedly increased Fos expression primarily in the spinal segments L5–S1 in the control rats, where the majority of bladder and urethral afferent fibres terminates. Fos-positive cells were located in the MDH, lateral dorsal horn (LDH), DCM and the lateral aspect of laminae V–VII. Compared to controls, Fos expression after spinal cord injury (SCI) occurred in a significantly greater number of neurones throughout the segments L3–S1 following induction of bladder reflexes. The greatest proportional increase in the number of Fos-positive cells occurred in L3–5 which normally receive only little afferent input from the urinary bladder. Cell numbers predominantly increased in the LDH and lateral lamina V–VII. The data are consistent with the concept of a neuroplastic reorganisation of spinal pathways after SCI. Unmasking of silent synapses or formation of new connections by afferent axonal sprouting caudal to the lesion, as evident from the increased numbers of cells expressing Fos after bladder distension, could be factors underlying the emergence of reflexogenic micturition in chronic SCI rats. Accepted: 27 May 1999     

Increased specific binding of [3H]diazepam in rat brain following chronic diazepam administration.

Male rats (175 g) were given 30 mg of diazepam in their food daily for 35 days. The animals became drowsy and ataxic from this high dose of drug. After the 35-day dosing, the rats were killed daily, and specific binding of [3H]diazepam and [3H]flunitrazepam was determined in synaptosomal preparations from these and corresponding control rats. On days 3, 4, 6, and 7 after the treatment period the specific binding and specific binding of [3H]diazepam was double that of the control binding and specific binding of [3H]flunitrazepam was 1.67 times that of control. The data indicate that very high doses of diazepam, given for long periods, cause increased specific binding of radiolabeled ligand to brain subfractions. The possible mechanisms and implications are discussed. When lower doses or shorter dosage regimens are used, increased binding is not observed.     

Modeling of exo-inulinase biosynthesis by Kluyveromyces marxianus in fed-batch mode: correlating production kinetics and metabolic heat fluxes

A metabolic heat-based model was used for estimating the growth of Kluyveromyces marxianus, and the modified Luedeking-Piret kinetic model was used for describing the inulinase production kinetics. For the first time, a relationship was developed to relate inulinase production kinetics directly to metabolic heat generated, which corroborated well with the experimental data (with R ² values of above 0.9). It also demonstrated the predominantly growth-associated nature of the inulinase production with Luedeking-Piret parameters α and β, having values of 0.75 and 0.033, respectively, in the exponential feeding experiment. MATLAB was used for simulating the inulinase production kinetics which demonstrated the model’s utility in performing real-time prediction of inulinase concentration with metabolic heat data as input. To validate the model predictions, a biocalorimetric (Bio RC1e) experiment for inulinase production by K. marxianus was performed. The inulinase concentration (IU/mL) values acquired from the model in were validated with the experimental values and the metabolic heat data. This modeling approach enabled the optimization, monitoring, and control of inulinase production process using the real-time biocalorimetric (Bio RC1e) data. Gas chromatography and mass spectrometry analysis were carried out to study the overflow metabolism taking place in K. marxianus inulinase production.

     

Increased nitric oxide production by neutrophils from patients with chronic granulomatous disease on trimethoprim-sulfamethoxazole.

Chronic granulomatous disease (CGD) is an inherited disease characterized by severe and recurrent bacterial and fungal infections. Phagocytic cells of CGD patients are unable to produce superoxide anion, and their efficiency in bacterial killing is significantly impaired. In these patients, the prophylactic and therapeutic validity of a long-term use of trimethoprim-sulfamethoxazole (TMP-SMX) has been well established. However a role of nitric oxide (NO) produced by phagocytic cells from CGD patients is unknown, and the mechanism of TMP-SMX in CGD is unclear. We have directly measured NO production in whole human blood by using 4,5-diaminofluorescein as a novel fluorescent indicator for intracellular NO. Intracellular NO production of gated neutrophils increased time dependently when stimulated by lipopolysaccharide (LPS) and calcium ionophore. Although all polymorphonuclear leukocyte (PMN) specimens from patients with CGD failed to generate hydrogen peroxide, NO production by CGD PMNs was significantly increased compared with that of control PMNs (p<0.05). TMP-SMX with LPS significantly increased compared with LPS-stimulated samples at clinical (n=5, p<0.05) and 10-fold clinical concentrations (n=5, p<0.01). TMP-SMX with LPS in CGD PMNs significantly increased the production of NO in comparison with the LPS stimulation at 10-fold clinical concentrations (n=5, p<0.05). In conclusion, our data indicate the possibility that NO production by neutrophils from patients with CGD treated with TMP-SMX has a role of bactericidal activity instead of O(2)(-) in host defense mechanism.     

Increased heat loss affects hibernation in golden-mantled ground squirrels

During hibernation at ambient temperatures (T(a)) above 0 degrees C, rodents typically maintain body temperature (T(b)) approximately 1 degrees C above T(a), reduce metabolic rate, and suspend or substantially reduce many physiological functions. We tested the extent to which the presence of an insulative pelage affects hibernation. T(b) was recorded telemetrically in golden-mantled ground squirrels (Spermophilus lateralis) housed at a T(a) of 5 degrees C; food intake and body mass were measured at regular intervals throughout the hibernation season and after the terminal arousal. Animals were subjected to complete removal of the dorsal fur or a control procedure after they had been in hibernation for 3-4 wk. Shaved squirrels continued to hibernate with little or no change in minimum T(b), bout duration, duration of periodic normothermic bouts, and food intake during normothermia. Rates of rewarming from torpor were, however, significantly slower in shaved squirrels, and rates of body mass loss were significantly higher, indicating increased depletion of white adipose energy stores. An insulative pelage evidently conserves energy over the course of the hibernation season by decreasing body heat loss and reducing energy expenditure during periodic arousals from torpor and subsequent intervals of normothermia. This prolongs the hibernation season by several weeks, thereby eliminating the debilitating consequences associated with premature emergence from hibernation.     

Increased prevalence of metabolic syndrome in patients with acne inversa

Background

Acne inversa (AI; also designated as Hidradenitis suppurativa) is a common chronic inflammatory skin disease, localized in the axillary, inguinal and perianal skin areas that causes painful, fistulating sinuses with malodorous purulence and scars. Several chronic inflammatory diseases are associated with the metabolic syndrome and its consequences including arteriosclerosis, coronary heart disease, myocardial infraction, and stroke. So far, the association of AI with systemic metabolic alterations is largely unexplored.

Methods and Findings

A hospital-based case-control study in 80 AI patients and 100 age- and sex-matched control participants was carried out. The prevalence of central obesity (odds ratio 5.88), hypertriglyceridemia (odds ratio 2.24), hypo-HDL-cholesterolemia (odds ratio 4.56), and hyperglycemia (odds ratio 4.09) in AI patients was significantly higher than in controls. Furthermore, the metabolic syndrome, previously defined as the presence of at least three of the five alterations listed above, was more common in those patients compared to controls (40.0% versus 13.0%; odds ratio 4.46, 95% confidence interval 2.02 to 9.96; P<0.001). AI patients with metabolic syndrome also had more pronounced metabolic alterations than controls with metabolic syndrome. Interestingly, there was no correlation between the severity or duration of the disease and the levels of respective parameters or the number of criteria defining the metabolic syndrome. Rather, the metabolic syndrome was observed in a disproportionately high percentage of young AI patients.

Conclusions

This study shows for the first time that AI patients have a high prevalence of the metabolic syndrome and all of its criteria. It further suggests that the inflammation present in AI patients does not have a major impact on the development of metabolic alterations. Instead, evidence is given for a role of metabolic alterations in the development of AI. We recommend monitoring of AI patients in order to correct their modifiable cardiovascular risk factors.