Increases in matrix metalloproteinase-9 and tissue inhibitor of matrix metalloproteinase-1 mRNA after cerebral contusion and depolarisation

Matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) play major roles in physiological extracellular matrix turnover during normal development and in pathological processes. In brain, increases in MMP activity occur, for example, in multiple sclerosis, Alzheimer's disease, and after head trauma. We examined MMP-9 and TIMP-1, -2, and -3 in events after head trauma. A time-course study was carried out using two different rat injury models, cerebral contusion and depolarisation. Brains were analysed by RT-PCR and in situ hybridisation. We observed a distinct and time-dependent upregulation of MMP-9 and TIMP-1 mRNA in ipsilateral cortical areas. MMP-9 mRNA levels were upregulated 1 day after cerebral contusion with a peak at Day 4. Depolarisation per se, which also occurs after traumatic brain injury, lead to delayed increase of MMP-9 mRNA, 4 days post application. At Day 14, MMP-9 mRNA levels were indistinguishable from controls in both models. TIMP-1 mRNA increases were observed in both models 4 hr after injury, and increased further at Days 1 and 4. At Day 14, mRNA levels declined and were no higher than control levels. No alterations in mRNA levels were noted for TIMP-2 or -3. Our results support earlier reports on MMP-9 involvement in brain injury. It also shows a role for TIMP-1 in the mechanisms of trauma, where depolarisation could be the mechanism responsible for this upregulation.     

The impact of adjustment for parity and mid-upper-arm circumference on sensitivity of symphysis-fundus height measurements to predict SGA foetuses in Mozambique

BACKGROUND: With a new symphysis-fundus height (SFH) growth chart, based on Mozambican women with ultrasound-dated singleton pregnancies, the aim was to examine the possibility to enhance sensitivity of predicting small for gestational age (SGA) newborns by attempts to adjust the chart for parity and for mid-upper-arm circumference (MUAC). METHODS: Two antenatal clinics were chosen in the suburban area of Maputo City. A cohort of 904 consecutively recruited antenatal clients was followed until birth. Gestational age was determined by ultrasound at enrolment. The growth of the SFH was measured every 2-3 weeks. Women with multiple pregnancy or with gestational age >21 weeks at enrolment were excluded. Attempts were made to adjust SFH measurements for parity and MUAC by developing a mathematical model to increase sensitivity of the SFH method to predict a foetus being SGA. RESULTS: Parous women had on average 0.5-1 cm higher SFH readings than nulliparous women. Women with a body mass index (BMI) <19 and women with BMI >27 had approximately 1 cm lower and 1 cm higher readings, respectively, compared with women of normal BMI. There was a significant correlation between BMI and MUAC (r = 0.621; P < 0.001). The usefulness of SFH measurements to predict SGA newborns was analysed. The sensitivity was 49%, the specificity was 66%, the positive predictive value was 14% and the negative predictive value, 93%. By using the correlation between BMI and MUAC we tried to find a simple and useful method to improve the sensitivity of SFH to detect SGA foetuses. By reducing the SFH measurement by 1 cm for women with MUAC >29 and by 1 cm for multiparous women the sensitivity raised to 65% at the expense of reducing the specificity to 51%. Using a linear function of BMI, MUAC and parity to adjust the SFH measurement for each individual woman, it was possible to get a sensitivity of 70% with a corresponding specificity of 56%. CONCLUSION: By using BMI, MUAC and parity, it might be possible to improve the sensitivity of the SFH growth chart in predicting newborn being SGA but mostly at the expense of specificity.     

Histamine provocation in young, awake children with bronchial asthma, using a fall in oxygenation as the only indicator of a bronchial reaction

Bronchial provocation with histamine was performed in 11 boys and 6 girls, age range 2.7-7.4 y, with unspecific respiratory symptoms or bronchial asthma, using a fall in oxygenation as the only indicator of a bronchial reaction. In addition to transcutaneous oxygen tension (tcPO2), transcutaneous carbon dioxide tension (tcPCO2) was continuously monitored during the provocation procedure in order to identify possible changes in ventilation. A fall of 20% or more in the tcPO2 below a "floating" baseline value, defined as the highest tcPO2 value between the inhalations of histamine up to that point, was regarded as indicating a significant bronchial reaction. One child was excluded from the study because of an "early, false-positive" reaction due to hyperventilation during the inhalation, verified by a decrease in the tcPCO2 followed by a compensatory period of hypoventilation, resulting in a fall of more than 15% in the tcPO2 after the inhalation of saline. In the vast majority of the children, however, the tcPO2 values remained stable during the first dose stages of saline and histamine, with either a gradual fall immediately before or a distinct fall in conjunction with the reaction. The mean reaction concentration was significantly lower in the group of children with clinical asthma, 0.74 mg/ml, compared with the group of children with unspecific respiratory symptoms, 2.00 mg/ml (p = 0.03). In conclusion, a 20% fall in the tcPO2 can be used as the only indicator of a bronchial reaction during bronchial provocation tests in young, awake children. Changes in ventilation evaluated by monitoring tcPCO2, makes it possible to distinguish between a fall in oxygen tension due to an early, "false" reaction as a result of hypoventilation and a "true" bronchial reaction.     

The effect of mesenteric lymphadenectomy and Kupffer cell depletion on bacterial translocation.

BACKGROUND: Infectious complications are associated with high morbidity in patients with short bowel syndrome and after small bowel transplantation. Bacterial translocation from the intestine is probably an essential factor in the genesis of these infections. In a model for bacterial translocation in the rat we examined the consequence of mesenteric lymphadenectomy and the depletion of Kupffer cells. MATERIALS AND METHODS: The effect of mesenteric lymphadenectomy was studied in two different models; in rats where a Thiry-Vella loop had been created from small bowel and in rats that had received a syngeneic small bowel transplant. To study the role of the Kupffer cells, rats with Thiry-Vella loops were treated intravenously with the Kupffer cell inhibitor gadolinium chloride. All animals were sacrificed on Day 3 postoperatively and the bacterial translocation to the mesenteric lymph nodes, liver, spleen, lung, and blood was evaluated. RESULTS: Removal of the mesenteric lymph nodes did not result in any increased bacterial translocation in animals with a Thiry-Vella loop. However, the inactivation of Kupffer cells with gadolinium chloride produced a more severe translocation to the liver, spleen, and lungs. After small bowel transplantation the bacterial translocation to the spleen was increased in animals without mesenteric lymph nodes. CONCLUSIONS: In the model of bacterial translocation from a defunctionalized loop of small bowel the inhibition of Kupffer cells will promote the systemic spread of the translocating bacteria. This indicates an important protective function of the Kupffer cells against translocating microbes.     

Incidence of CSF abnormalities in siblings of multiple sclerosis patients and unrelated controls

We found that 19% (9/47) of healthy siblings of patients with clinically definite multiple sclerosis had an intrathecal immunological reaction with two or more 2 CSF-enriched oligoclonal bands (OCBs), in contrast to (4%) (2/50) unrelated healthy controls. Furthermore, in this group of nine healthy sibs the measles CSF IgG antibody titers were higher than that of the other sibs and that of controls. There were also differences in the serum titers for measles IgG antibody, which were higher in the group of all healthy sibs than in healthy volunteers, and (as with CSF titers) higher in the subgroup of healthy sibs with two or more 2 CSF-enriched OCBs than the other sibs. Thus a significant proportion of healthy siblings to MS patients have a partially hyperimmune condition similar to that occurring in MS, which in 19% manifested itself as an OCB reaction, in 9% as increased CSF measles IgG antibody titers, and in 21% as increased serum measles IgG antibody titers, these phenomena tending to occur in the same individuals. This condition is characterized by CSF-enriched OCBs with undefined specificity, although some increased antiviral reactivity is found both in the serum and CSF. While it needs further characterization, a genetic trait interacting with common infections is suggested. The recurrence risk of this condition is approximately five times higher than the 3-4% recurrence risk for manifest MS reported for sibs.     

Marked heterogeneity of human skeletal muscle lipolysis at rest

In this study, variations in lipolysis among different muscle groups were examined by measuring local net glycerol release in vivo in healthy, normal-weight subjects (n = 11) during rested, postabsorptive conditions. Microdialysis of the gastrocnemius, deltoid, and vastus lateralis muscle regions revealed that extracellular glycerol concentrations of these three muscle regions were 84.7 +/- 6.7, 59.7 + 7.3, and 56.4 +/- 7.5 micro mol/l, respectively, and the arterial plasma glycerol concentration was 44.8 +/- 2.3 micro mol/l (P = 0.0003-0.006, gastrocnemius vs. others). Local tissue blood flow, as measured by Xe clearance, did not differ among the regions. Net glycerol release was significantly higher in gastrocnemius muscle than in the two other regions. There were no regional differences in glycerol uptake when studied during glycerol infusion. Gastrocnemius muscle showed a dominance of type 1 fibers (70%), whereas the vastus lateralis muscle had equal distribution of fiber types (P = 0.02). No differences in intramuscular triaclyceride content, perimuscular fat, or the adipocyte-specific protein perilipin were observed among the muscle regions. Triglyceride turnover in the gastrocnemius muscle was 3.3 + 1.4% over 24 h, which is about 10 times more rapid than the turnover rate in subcutaneous adipose tissue (P < 0.01). Thus there were marked differences in lipolytic activity among skeletal muscle groups at rest, possibly reflecting variations in fiber type.     

Combined treatment with calcitonin and 1,25-dihydroxyvitamin D3 for osteoporosis in women

Summary Twenty-two middle-aged women with severe osteoporosis were treated for 2 years with either 0.5 mg of synthetic human calcitonin subcutaneously three times per week combined with 0.5 g of calcitriol and 0.5 g of calcium per day orally or calcium only. The treatment with calcitonin plus calcitriol (12 patients) resulted in a significantly increased calcium absorption rate. The mean values for serum phosphate did not change during the treatment period and the mean values did not differ between the treatment groups, but the serum calcium and urinary Ca/Cr ratio increased somewhat in the group given the combined treatment. There was no evidence that the combined treatment improved the bone density in this study. It is possible that calcitriol, instead of increasing the effect of calcitonin by suppression of the parathyroid, might have counteracted its effect by increasing the bone resorption.     

Selenium status in females with occupational cervico-brachial complaints

Summary A hypothesis that selenium deficiency predisposes the development of occupational cervicobrachial complaints was tested in 134 females working in an assembly factory, with constrained work postures and repetitive work tasks. Seventeen subjects, who reported intake of selenium tablets, had higher plasma selenium levels than the others (104 vs 89 g/l, P = 0.01). Among those who did not take selenium tablets, 21% reported symptoms from the upper back during the last 7 d, 21% from the neck, 38% from the shoulders, 15% from the elbows, and 27% from the hands. Subjects with pain in their elbows had slightly, but significantly, lower plasma selenium levels than asymptomatics (84 vs 90 g/l, P = 0.048). For the other anatomical regions, there were no statistically significant differences. Thus, there was no major association between selenium status and pain; conclusions regarding any minor association must await further studies.