Study of low salt diet in hypertensive patients with chronic kidney disease.

INTRODUCTION: The efficacy of blood pressure (BP) reduction with salt restriction in CKD subjects and its sustainability is not well established. METHODS: We enrolled 75 hypertensive patients with CKD into one-month salt restricting diet. 24-hour urinary sodium and potassium was measured to verify their salt intake followed by 1½ year follow-up. RESULTS: Their creatinine clearance was 43 ± standard deviation 33ml/min/1.73m2. Urinary Na excretion (24HUNa) was 173±129mmol/day, reducing to 148±81 by 31±6 day. Mean, systolic and diastolic BP (MBP, SBP, DBP) were reduced from 102±9 to 97±11 (p<0.001), 148±10 to 139±16 (p<0.001), 78±12 to 75±12 mmHg (p=0.012) respectively. Moderate correlations were shown between reductions in 24-hour urinary Na and MBP, SBP, DBP: r=0.366, 0.260, 0.365; p=0.001, 0.025, 0.001; whereas 24-hour urinary Na-K ratio showed mild correlation. Subjects have some tendency to drift back to previous Na intake profile in follow-up and thus repetitive education is necessary. In subanalysis, 34 subjects with baseline 24HUNa >150 mmol/day, benefited significantly with MBP, SBP, DBP reduction from 102±9 to 95±9 (p=0.001), 146±10 to 135±14 mmHg (p=0.001), 80±11 to 75±11 mmHg (p=0.002) in line with 24HUNa reduction from 253±154 to 163±87mmol/day (p=0.004) and urinary protein-creation ratio reduction from geometric mean of 95 to 65 g/mol. Thirty five subjects with 24HUNa reduction of >20mmol/day have significant reduction in MBP, SBP, DBP: -8 vs -2, -15 vs -4, -5 vs -2 mmHg (p=0.027, 0.006, 0.218) and urinary protein-creatinine ratio: -82 vs 2g/mol (p=0.030) compared to the other forty subjects. CONCLUSION: Quantification of 24-hour urinary Na helps in predicting potential antihypertensive effect with dietary salt reduction of CKD subjects. Salt restriction reduces BP especially in patients with estimated daily sodium intake of >150mmol/day. Reduction in sodium intake beyond 20mmol/day reduced both BP and proteinuria.

Serum calcium concentration affects signal changes on diffusion-weighted imaging in hypoglycemic encephalopathy.

BACKGROUND AND PURPOSE: Abnormal signals in brain DWI may appear in patients with HE. The aim of this study was to compare the clinical condition and various physiologic factors between patients with HE with and without abnormal signal intensity changes on DWI. MATERIALS AND METHODS: We retrospectively enrolled patients with HE who underwent brain DWI studies from January 2002 to November 2010. A diagnosis of HE was defined as low serum glucose levels (<50 mg/dL) with alteration of consciousness. Several clinical conditions and physiologic parameters were compared between patients with and without abnormal signals on DWI, including consciousness levels; outcome; body temperature; blood pressure; and serum levels of glucose, calcium, sodium, blood urea nitrogen, and creatinine. RESULTS: Nine patients with HE were included, and 3 of them (33%) had abnormal signals on brain DWI. There was a trend toward serum calcium concentrations being lower in patients with normal findings on DWI studies compared with patients with abnormal DWI signals (7.6 ± 1.7 versus 9.4 ± 0.7 mg/dL, P = .07). Serum glucose concentration, duration of hypoglycemia, consciousness levels, other physiologic parameters, and clinical outcome did not reveal any differences between the 2 groups. CONCLUSIONS: One-third of patients with HE had abnormal signals on brain DWI, and patients with low serum calcium levels may be less likely to present with abnormal DWI signals.

In vitro and in vivo evaluations of topically applied capsaicin and nonivamide from hydrogels.

The purpose of this study was designed to investigate the in vitro and in vivo skin absorption of capsaicin and nonivamide from hydrogels. Various commercialized creams of capsaicin were also compared with hydrogels. Both skin stripping technique and Mexameter were applied to evaluate the level of capsaicin and nonivamide retained in stratum corneum (SC) and skin erythema in vivo. The partition of drug between skin and the hydrogel matrix was considered to play an important role in the permeation process. The in vitro permeation of capsaicin from hydrogels depends on the physicochemical nature and the concentration of the polymer used. The incorporation of nonionic Pluronic F-127 polymer into hydrogels resulted in a retarded release of capsaicin. On the other hand, the in vitro capsaicin permeation showed higher levels in cationic chitosan and anionic carboxymethyl cellulose (CMC) hydrogels than cream bases. The permeation of nonivamide was retarded at the late stage of in vitro application. The inter-subject variation was more significant in the in vivo study than in vitro skin permeation experiments. The cream induced in vivo skin erythema depending on the drug concentration, however, the dose-dependence was not observed in hydrogels. Nonivamide-treated skin showed stronger erythema than capsaicin-treated skin. The present study indicates that there is a moderate correlation between in vitro skin permeation and in vivo erythema responses of topically applied capsaicin and nonivamide. The correlation between drug amount in SC and skin erythema test in vivo was also observed.

Effect of liposomes and niosomes on skin permeation of enoxacin.

The skin permeation and partitioning of a fluorinated quinolone antibacterial agent, enoxacin, in liposomes and niosomes, after topical application, were elucidated in the present study. In vitro percutaneous absorption experiments were performed on nude mouse skin with Franz diffusion cells. The influence of vesicles on the physicochemical property and stability of the formulations were measured. The enhanced delivery across the skin of liposome and niosome encapsulated enoxacin had been observed after selecting the appropriate formulations. The optimized formulations could also reserve a large amount of enoxacin in the skin. A significant relationship between skin permeation and the cumulative amount of enoxacin in the skin was observed. Both permeation enhancer effect and direct vesicle fusion with stratum corneum may contribute to the permeation of enoxacin across skin. Formulation with niosomes demonstrated a higher stability after 48 h incubation compared to liposomes. The inclusion of cholesterol improved the stability of enoxacin liposomes according to the results from encapsulation and turbidity. However, adding negative charges reduced the stability of niosomes. The ability of liposomes and niosomes to modulate drug delivery without significant toxicity makes the two vesicles useful to formulate topical enoxacin.

Capsaicin and nonivamide as novel skin permeation enhancers for indomethacin.

The study was conducted in vitro to investigate the changes of indomethacin transdermal permeation pretreated by capsaicin and nonivamide, two compounds chemically similar to Azone. The combined effect of low frequency ultrasound (20 kHz) and enhancers on the indomethacin permeation was also evaluated. The experimental data demonstrated that capsaicin and nonivamide significantly enhanced the flux of indomethacin across nude mouse skin. Enhancement effects of both analogues were very similar and depended predominantly on the concentration tested. Histological examination coupled with visual scores indicated the safety of capsaicin and nonivamide on skin structure. Simultaneous application of ultrasound and enhancers significantly increased skin permeation of indomethacin compared with either ultrasound or enhancers alone. Better effect was obtained by the combination with capsaicin than nonivamide.

Modulation of cytochrome P450-dependent monooxygenases in streptozotocin-induced diabetic hamster: II. Reverse role of insulin in P450 activity and defluorination.

BACKGROUND: Metabolic activities of cytochrome (cyt) P450-dependent monooxygenase could be modulated by diabetic state in experimental diabetic animals. The purpose of this study is to validate the effect of insulin on the modulation of the metabolic activity of cyt P450 and the defluorination ability to inhalational anesthetics in diabetic animals. METHODS: Diabetic state in golden Syrian hamsters was achieved by intraperitoneal injection of streptozotocin 40 mg/kg once a day for 4 days. After stabilization of diabetic state for 6 weeks, a regimen of insulin treatment given subcutaneously was carried out. Metabolic activities of cyt P450 were assessed by the reaction with benzo(a) pyrene, pentoxyresorufin, aniline and erythromycin (specific substrates). The metabolic activities of cyt 1A1, 2B1, 2E1 and 3A4 respectively in a NADPH-generating system in microsomal preparations of the diabetic hamsters were observed before and after insulin treatment, and were compared with the control group. The ability of defluorination was evaluated by measuring the free fluoride metabolites after incubating the microsomes with enflurane in diabetic and insulin-treated hamsters. Contents of cyt P450 isozymes were measured by electrophoresis and immunoblotting before and after insulin treatment. Pathological features of hepatocytes in diabetic hamsters were evaluated microscopically before and after insulin treatment. RESULTS: The defluorination of enflurane and activity of aniline hydroxylase (cyt 2E1) were successfully induced by diabetic state (P < 0.01). The pentoxyresorufin O-dealkylase (cyt 2B1) was inhibited nearly 50% in the diabetic hamster liver when compared with that of control (P < 0.01). While the activities of benzo(a)pyrene hydroxylase (cyt 1A1) and the erythromycin N-demethylase (cyt 3A4) were basically unaffected by diabetes, alterations in content of cyt P450 were parallel to the alterations in enzyme activities. Microscopically, diabetes induced vacuolization with fatty droplets in the hepatocytes. After treatment with insulin injection, the enzyme activities, protein content and pathologic features returned to the baseline similar to the control. CONCLUSIONS: Our data demonstrated that under diabetic state, metabolic activities of cyt P450 and its extent of defluorination would be polymorphically modulated. After administration of insulin, the activities of cyt P450 and defluorination of enflurane returned to baseline as the blood sugar level had been normalized. This could remind the clinicians of the importance of insulin treatment in the potential drug-to-drug interactions in the diabetic patients.

Estimation of costs due to hospitalization for first-ever stroke patients in northern Taiwan.

BACKGROUND: The need for healthcare services and the related costs for stroke patients may rise steadily in the future. Even with the predictable and substantial burden of stroke, little effort has been devoted to measuring the population-based direct medical and nonmedical costs in Taiwan. METHODS: Data from the study "Epidemiological Study of Stroke, Diabetes, and Cardiovascular Disease," which included 8,705 people older than 35 years of age, and the study "Costs of Stroke," which included 660 first-ever stroke patients, were used for the cost calculations. The cost of hospital care for stroke patients was obtained in two steps. First, the incidence of stroke and readmissions within one year were tallied; the sum was then multiplied by the average length of stay. Second, the total medical and nonmedical costs were divided by the sum obtained from step 1. The resulting quotient obtained was the cost of hospital care for stroke patients per day. RESULTS: There were 6,691 incidents of stroke and stroke-related readmissions in 1995 (4,041 men and 2,650 women). The total person-days of hospital stay were 233,569 days (144,264 for men and 89,305 days for women). The average medical and nonmedical costs of hospital care per person-day was US $251.4 (NT $6,788 at an exchange rate of US $1 = NT $27). Cost for men (US $287, NT $7,749) was more than for women (US $208, NT $5,616). The total direct costs of hospital care were US $58,710,000 (NT $1,585,000,000) in 1995. CONCLUSIONS: An average of US $1,682,000 (NT $45,410,000) in hospital care costs for stroke could have been saved in 1995 if the person-day stay had been decreased by only one day.

Effect of trilinolein on superoxide dismutase activity and left ventricular pressure in isolated rat hearts subjected to hypoxia and normoxic perfusion.

Oxygen-derived free radicals have been implicated in the development of myocardial injury during hypoxia/reperfusion. Antioxidants can effectively inhibit the formation of free radicals and ameliorate the myocardial damage which may occur during hypoxia/reperfusion. Trilinolein is a triacylglycerol recently purified from the traditional Chinese medicinal plant Panax pseudo-ginseng. It has linoleic-acid residues as the only type of fatty acid residue in all three esterified positions of the triacyglycerol. It has been proposed that decreased endogenous superoxide dismutase (SOD) activity may contribute to free radical-mediated reperfusion injury of the ischemic myocardium. In the present study, when isolated rat hearts were subjected to hypoxia for 10, 30, 60 and 90 min without normoxic perfusion, a significant decrease in Mn-SOD activity was shown throughout the period of hypoxia, whereas the Cu.Zn-SOD activity was increased at 10 and 30 min but was not different from the baseline at 60 and 90 min of hypoxia. In rat hearts pretreated with 10(-7) mol/l trilinolein and subjected to 60 min of hypoxia without normoxic perfusion, Cu.Zn-SOD was augmented compared with baseline and compared with hearts subjected to 60 min of hypoxia without trilinolein, whereas Mn-SOD activity was still reduced compared with baseline, although less so than after 60 min of hypoxia without trilinolein. Pretreatment with trilinolein was associated with better preservation of left ventricular function during hypoxia and more rapid return to recovery during normoxic perfusion. This myocardial protective effect may be related to an antioxidant effect through potentiation of SOD, particularly Cu.Zn-SOD during hypoxia.

Correlation between sonography and pathology in thyroid diseases.

Ultrasonography was performed on the thyroid glands of 47 patients with various thyroid diseases, in a fresh state, immediately following operation. The thyroid glands were then sectioned along the plane of the most significant sonographic changes. The pathologic changes of the sectioned plane were observed and compared with the sonographic changes. In nodular goiter, the sonographic changes were usually heterogeneous. The margin was either well-defined or ill-defined, and cystic changes might play a minor or major part in the thyroid nodules. In follicular adenoma, the changes were isoechoic in adenoma with embryonal type follicles and hyperechoic in adenoma with colloid type follicles. In adenoma of the oxyphilic cells, the echogenicity was somewhat greater in the hemorrhagic part compared to the area with oncocytic change only. In papillary carcinoma, the lesions usually manifested as well-limited, heterogeneous, hypoechoic nodules. Cystic degenerations were frequently noted. There were discrete particles corresponding to microcalcification in 4 out of 6 cases. In follicular carcinoma, the sonographic changes also showed well-limited nodules. However, the echogenicity was not decreased as much as in papillary carcinoma, and it could be either homogeneous and isoechoic, or hypoechoic. Relatively large particles with an acoustic sign, which corresponded to calcification, were noted in 2 out of 4 cases. In medullary carcinoma, the lesion was well-limited and hypoechoic. The particles present in sonography corresponded to calcification in the amyloid. In Graves' disease, the main sonographic change was a diffusely homogeneous, isoechoic or hypoechoic lesion. Cystic change was rarely present. Dispersed particles were rarely present and corresponded to fibrosis in the thyroid tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Quantitative topographic electrophysiology and functional neurologic status in right middle cerebral artery infarction.

Thirteen patients with clinically and radiographically defined right middle cerebral artery infarction were studied using EEG, quantitative electroencephalographic (QEEG) spectra, and multi-channel evoked potentials. The purpose of this effort was to develop QEEG rules that related to the patient's neurologic status. Three QEEG relative delta spectral patterns were identified in the right hemisphere which related to neurologic residua. These include limited perisylvian involvement, mixed involvement of perisylvian and extrasylvian regions, and extrasylvian involvement only. While there were parallels between QEEG spectral patterns and auditory, visual and somatosensory evoked potentials, there were modality specific features consistent with functional differences.

Infarction of the superior temporal gyrus: a description of auditory evoked potential latency and amplitude topology.

P1 and N1 of the cortical auditory evoked potential (AEP) were studied with multiple electrodes in 10 normal subjects and 6 patients with left middle cerebral artery infarction. Patients were selected based on neurological examination and on CT scans showing both (1) infarction limited to the vascular territory and (2) involvement of posterior portion of superior temporal gyrus. Waveforms recorded from C3, Cz, and C4 were examined for peak latency and amplitude of P1 and N1 on all subjects. Topographic displays of amplitude over P1 and N1 latency ranges were also examined. In normals, P1 was identified in 9 of the 10 subjects at all three electrode sites. In patients, P1 was identified at C3 in only 1 of the 6. N1 was present at all three electrodes in the 10 normal subjects and in 5 of the 6 patients. The remaining patient had N1 at C4 and Cz only. Examination of amplitude topology showed as asymmetric evolution of P1 and N1 in the patients. This asymmetry was not present in normals. The results of this study are consistent with theory that P1 arises from primary auditory cortex. Results further suggest multiple generators for N1. Additional study correlating topographic display from multichannel recordings with CT or MRI in brain-injured patients may bring more insight into N1 generators.

Erb's and cervical somatosensory evoked potentials: correlations with body size.

Median and ulnar Erb's (N9) and cervical (N13) somatosensory evoked potentials were correlated with height, arm span, arm length, and Erb's length. All body measurements had high correlations with the N9 and N13 latencies. The highest correlation was obtained between the N9 latency and Erb's length. The N13 latency was correlated higher with height than with arm length. The data suggest that height can be used to construct normogram correlating with the N13 latency.