Sandra Regina R. Lucas

Functional and morphometric evaluation of offspring kidney after intrauterine undernutrition

Abstract  Pregnant rats were subjected to 50% food restriction during the first or the second half of pregnancy, or throughout pregnancy. The effects of intrauterine food restriction, on kidney function and morphometry were studied in newborn and adult (3 months) offspring. No differences in glomerular diameter were observed in newborn restricted rats compared with controls. The number of glomeruli was significantly lower both in newborn and 3-month-old restricted rats. However, glomerular diameter was increased in 3-month-old rats, which suggests that hypertrophic stimuli were present. The medulla/cortex ratio increased in adult rats submitted to food restriction during pregnancy, a finding that agrees with the preserved sodium and acid excretion, and the normal osmolar and free water clearance observed in these groups. These results show that the reduction in glomerular number is still present 3 months after birth in the progeny of mothers submitted to severe food restriction during pregnancy, suggesting impairment of glomerulogenesis even after birth. Intra utero undernutrition can be regarded as an experimental model of glomerular hypertrophy.

Intrauterine undernutrition—renal and vascular origin of hypertension

OBJECTIVE A large number of clinical and experimental studies supports the hypothesis that intrauterine undernutrition is an important determinant of hypertension, coronary heart disease and non-insulin-dependent diabetes in the adult offspring. In this review, the renal and vascular repercussions of maternal undernutrition are emphasized, and the physiopatologic mechanisms discussed. The origin of hypertension is detailed based upon the findings of kidney functional parameters and endothelium function studies. A working model linking hypertension to intrauterine undernutrition is proposed.

L-Arginine effects on blood pressure and renal function of intrauterine restricted rats

Abstract. We have previously demonstrated that 3-month-old rats submitted to 50% intrauterine food restriction showed a decreased number of nephrons with increased glomerular diameter, a fact that suggests compensatory hypertrophy. In the present study, we extended the investigation and performed serial blood pressure measurements and renal function evaluation in 8- and 12-week-old rats submitted to 50% intrauterine food restriction (groups R8 and R12) and in age-matched control rats (groups C8 and C12). After weaning, six to eight animals from each group received oral supplements of 2% L-arginine (L-arg) solution for 4 or 8 weeks (groups CA8, CA12, RA8, RA12). Our findings showed that mean blood pressure (MBP), which was significantly increased from 8 weeks on in R rats, markedly decreased after L-arg supplementation. In control animals, no alterations in MBP were observed with L-arg. Proteinuria was within normal limits in all groups studied but L-arg caused a significant decrease in this parameter in both the RA8 and RA12 groups. Glomerular filtration rate (GFR, ml/min per kg) was significantly decreased in the C8 control group (3.75±0.12) and in both restricted groups R8 and R12, (2.47±0.13 and 3.76±0.16, respectively) compared with the C12 group (6.09±0.31; P<0.05 for all comparisons). L-Arg caused an increase in GFR only in the younger groups, C8 and R8. In a separate set of experiments, acetylcholine (ACh)-induced relaxation was examined in mesenteric arteries. The R12 group showed a significant impairment of the response to ACh, which returned to normal values after L-arg supplementation. Urinary excretion of NOx (NO3– + NO2–) was significantly decreased in 8- and 12-week-old food-restricted rats relative to control rats. Our data indicate that, besides the known decrease in absolute nephron number, disturbances in the production/sensitivity to the L-arg–nitric oxide system may contribute to the early appearance of hypertension in the offspring of mothers submitted to significant food restriction.

Acute Effect of Nasal Continuous Positive Air Pressure on the Ventilatory Control of Patients with Obstructive Sleep Apnea

Background: Sleep fragmentation can decrease the awake ventilatory control. Since patients with obstructive sleep apnea (OSA) patients exhibit sleep fragmentation linked to respiratory events, their ventilatory control could be impaired. However, most of these patients are also obese, which could conversely increase the ventilatory control. The effect of nasal continuous positive airway pressure (CPAP) on the awake ventilatory control in normocapnic OSA patients is unclear. Objectives: To study the acute effect of nasal CPAP on the awake ventilatory control in normocapnic OSA patients. Methods: 12 normocapnic OSA patients, with an apnea/hypopnea index (AHI) >15 with moderate obesity (body mass index: 33.5 kg/m2) and normal pulmonary function tests were submitted to two polysomnography studies (diagnostic and for CPAP titration). Before and after 3 consecutive nights of nasal CPAP we analyzed the hypersomnia score and the ventilatory and the mouth occlusion pressure (P.1) responses at rest (breathing room air and a mixture of 8% CO2 + 40% O2). Results: The respiratory drive of OSA patients as evaluated by P.1 was in the range of the controls of our laboratory. After nasal CPAP, a significant decrease in AHI (mean: 51.9–9.4/h) and arousal (mean: 88.7–43/h) occurred, as well as improvement in nocturnal oxyhemoglobin. There was a marginal increase in ΔVE/ΔPETCO2 (mean: 1.41–1.87 liters/min/ mm Hg, p = 0.09) and a significant rise in P.1/ΔPETCO2 (mean: 0.29–0.43 cm H2O/mm Hg), a better indicator of ventilatory drive. Conclusions: Normocapnic OSA patients increased their awake ventilatory drive response to a hypercapnic and hyperoxic mixture with the use of 3 consecutive nights of nasal CPAP.

Effects of intrauterine food restriction and long-term dietary supplementation with L-arginine on age-related changes in renal function and structure of rats.

We have previously demonstrated that restricting intrauterine food by 50% in 3-mo-old rats produced lower nephron numbers and early-onset hypertension, the latter being normalized by l-arginine administration. In 18-mo-old rats, such restriction increased glomerulosclerosis. In this study, we expanded our investigation, evaluating functional, morphologic, and immunohistochemical parameters in intrauterine-food-restricted 18-mo-old rats, either receiving l-arginine (RA18) or not (R18). Age-matched, non-food-restricted controls were assigned to similar groups with l-arginine (CA18) and without (C18). After weaning, l-arginine was given daily for 17 mo. No functional or morphologic changes were observed in C18 rats. The R18 rats developed early-onset hypertension, which persisted throughout the observation period, as well as significant proteinuria from 12 mo on. In RA18 rats, l-arginine decreased both blood pressure levels and proteinuria, and glomerular diameter was significantly smaller than in R18 rats (115.63 ± 2.2 versus 134.8 ± 1.0 μm, p < 0.05). However, in RA18 rats, glomerular filtration rate remained depressed. Although l-arginine prevented glomerulosclerosis (R18 = 14%, RA18 = 4%; p < 0.05), glomerular expression of fibronectin and desmin was still greater in RA18 rats than in controls. Our data show that, although l-arginine prevented hypertension and proteinuria, glomerular injury still occurred, suggesting that intrauterine food restriction may be one of the leading causes of impaired renal function in adult life.

Differences between remaining ability and loss of capacity in maximum aerobic impairment.

In the evaluation of exercise intolerance of patients with respiratory diseases the American Medical Association (AMA) and the American Thoracic Society (ATS) have proposed similar classification for rating aerobic impairment using maximum oxygen uptake (VO2max) normalized for total body weight (ml min-1 kg-1). However, subjects with the same VO2max weight-corrected values may have considerably different losses of aerobic performance (VO2max expressed as % predicted). We have proposed a new, specific method for rating loss of aerobic capacity (VO2max, % predicted) and we have compared the two classifications in a prospective study involving 75 silicotic claimants. Logistic regression analysis showed that the disagreement between rating systems (higher dysfunction by the AMA/ATS classification) was associated with age > 50 years (P < 0.005) and overweight (P = 0.04). Interestingly, clinical (dyspnea score) and spirometric (FEV1) normality were only associated with the VO2max, % predicted, normal values (P < 0.01); therefore, in older and obese subjects the AMA/ATS classification tended to overestimate the aerobic dysfunction. We conclude that in the evaluation of aerobic impairment in patients with respiratory diseases, the loss of aerobic capacity (VO2max, % predicted) should be used instead of the traditional method (remaining aerobic ability, VO2max, in ml min-1 kg-1).

Estudo da eficácia e tolerabilidade do salmeterol comparativamente ao salbutamol em pacientes com asma brônquica

B2-agonists are considered one of the cornerstones of the asthma therapy, but their short action requires frequent administration and an association with other broncodilators. The development of long-acting b2-agonists may represent an important improvement in asthma treatment. PURPOSE: The present study was designed to assess the efficacy and safety of inhaled salmeterol compared to salbutamol in patients with mild-to-moderate asthma. METHODS: After the two run-in weeks, the patients received either salmeterol 50mg twice a day or salbutamol 200 mg four times a day, over a four week period, following a double blind, parallel group study. Sixty patients had the following inclusion criteria: FEV1 > 50% or PEFR over the past seven days >50% of predicted normal; reversibility of FEV1 >15%; symptoms scores >2 (score 0 and 5) in 4 of the last seven days or PEFR variation >15% . RESULTS: Seven patients discontinued the protocol (see methods). Of the 53 analyzable patients, 25 were of the salmeterol group and 28 of the salbutamol group. Our results showed that in the run-in period there were not differences among the groups comparing the values of FEV1 in % predicted, morning PEFR and asthma symptoms scores. The improvement rate of morning FEV1 and PEFR in patients who received salmeterol was significantly higher (p<0.05) compared to the patients who received salbutamol, for two and four weeks of treatment. Also, the salmeterol group have shown reduction of the symptoms in the nocturnal period(significantly in the first fortnight of treatment) demonstrated by the significative increase in the symptoms improvement rate when compared salmeterol and to salbutamol groups. The number of rescue medication inhaled, side effects, heart rate, blood pressure, serum potassium dosage and electrocardiograms, did no show significative differences between the groups. CONCLUSION:This study showed that in mild to moderate asthmatic patients, salmeterol in the dosage of 100mg/day raised the FEV1 and the morning PEF and led to pronounced decrease in the nocturnal symptoms as compared to salbutamol. The side effects were similar.

Histometric evaluation of dental alveolar repair in malnourished rats in the intrauterine or postnatal phase

OBJECTIVE Nutritional aggravations during pregnancy or during the early stages of postnatal development can impair bone development; thus, we aimed to assess the effects of food restriction on the dental alveolar bone repair process using histometric analysis. DESIGN Thirty-six Wistar rats were divided into three groups: (C) 12 pups were obtained from control mothers with food intake at ease; (GR) 12 pups from mothers subjected to 70% food restriction during pregnancy; (PNR) 50% of maternal food restriction during lactation and 50% of restriction for the 12 pups after weaning. At three months of age, the upper right incisor was extracted from the pups. After 14 or 28 days, the pups were sacrificed for evaluation of newly formed bone area (NB) and total bone area (TA) in the medial and apical thirds of the alveolus. RESULTS In the apical third of the alveolus, the ratio of NB/TA was greater at 28 days for all groups and there was no damage to any of the groups. In the medial third, the ratio was higher at 28 days for the C and GR groups. The PNR group did not show an evolution of alveolar dental repair. Compared between the thirds, all groups exhibited a higher percentage of newly formed bone in the medial third area, at any time point after surgery. CONCLUSIONS The percentage of the total alveolar area covered by newly formed bone (NB/TA) revealed a late preference in the process of alveolar repair in the medial third, although only in the PNR group.