[The influence of chronic intermittent hypoxia on hypothalamic-somatotropic axis in rats].

Objective: To investigate the effects of chronic intermittent hypoxia on somatotropic axis hormone levels in rats. Methods: Mature male Wistar rats were exposed to air or intermittent hypoxia randomly.The serum levels of growth hormone-releasing hormone (GHRH), growth hormone (GH) and somatostatin (SS) were measured before exposure, at the 4th, 8th, and 12th week after exposure. Different hormone levels in two groups were compared and analyzed. Results: Compared with the control group, GHRH levels in chronic intermittent hypoxic group showed a significant decline at the 4th week [(732.77±46.99)pg/ml vs. (893.59±40.00) pg/ml, P<0.05], while SS levels at the 8th week [(30.71±2.27) pg/ml vs. (44.69±3.36) pg/ml, P<0.05] and GH levels at the 12th week [(1.20±0.29) ng/ml vs. (2.06±0.13) ng/ml, P<0.05] were similarly reduced. As the duration of intermittent hypoxia was prolonged, the GHRH levels did not decrease further [4th week (732.77±46.99) pg/ml vs. 8th week (607.54±131.61) pg/ml vs. 12th week (730.05±40.63) pg/ml, P>0.05].However, the serum SS levels decreased further from the 8th week to the 12th week [(30.71±2.27) pg/ml vs. (24.41±4.06) pg/ml, P<0.05]. Conclusion: Chronic intermittent hypoxia might inhibit the function of somatotropic axis. Hypothalamic hormones are the earlyonesto be influenced, thereafter the entire axis.

[Aesthetic reconstruction strategy for postburn facial scar and its clinical effect].

OBJECTIVE: To explore the aesthetic reconstruction strategy for postburn facial scar and its clinical effect. METHODS: Three hundred and forty-two patients with postburn facial scars were hospitalized from January 2000 to December 2015. Local expanded flap or deltopectoral expanded flap was used for reconstruction according to the location and size of the facial scar. The forehead expanded flap could be chosen for the scar in dorsum nasi or inferior eyelid. The local expanded flap was chosen when the scar width was smaller than 5 cm in cheek, chin, and marginal mandible region. The expanded deltopectoral flap was chosen when the scar width was larger than 5 cm in cheek, chin, and marginal mandible region or the scar contracture was too serious to cause displacement of lips, nose, or eyelid, and the wound width was larger than 5 cm after release. The facial scars of 82 patients, with size ranged from 6.0 cm×2.5 cm to 15.0 cm×10.0 cm, were reconstructed with expanded local flaps. The facial scars of 260 patients, with size ranged from 8.0 cm×7.0 cm to 38.0 cm×13.0 cm, were reconstructed with expanded deltopectoral flaps. After expansion of 2 to 6 months, the facial scars were excised and completely released first of all. The transfer way of local flap and size of deltopectoral flap with pedicle were designed according to the size and shape of the wound. Three weeks after transfer of deltopectoral flap, flap delay procedure was conducted. One week later, the pedicle was severed from the flap to reconstruct the remaining scar. Anti-scar medicine, laser therapy, and elasticized fabric were used postoperatively on the scars in both donor and recipient sites. RESULTS: During the postoperative follow-up for 3 to 12 months, the flaps of 40 out of 82 cases reconstructed with expanded local flaps were in good color and texture. Before 2008, mild scar hyperplasia was observed in the incision of 19 patients; with application of laser after 2008, the number of patients with scar hyperplasia was decreased. During the postoperative follow-up for 3 to 12 months, the flaps of 90 out of 260 cases reconstructed with expanded deltopectoral flaps were in good color and texture. The expander was exposed from the incision in 15 patients, while it did not affect the later treatment. Nine unilateral flaps showed poor blood circulation at the distal end, and they were healed after dressing change. In the early phase, necrosis was observed in one flap after transfer, and it was healed after transplantation of free skin graft. Scar hyperplasia was observed in the chest donor site of one patient, and it was improved after laser therapy. CONCLUSIONS: Postburn facial scar could be reconstructed with local or deltopectoral flaps, following the principle of similarity. The expansion could increase the size of the flaps, reduce the thickness of the flaps, and lower the donor site damage.

Effects of RuPeng15 Powder (RPP15) on Monosodium Urate Crystal-Induced Gouty Arthritis in Rats.

RuPeng15 Powder (RPP15) is a herbal multicompound remedy that originates from traditional Tibetan medicine and possesses antigout, anti-inflammatory, and antihyperuricemic properties based on the traditional conceptions. The present study was undertaken to evaluate the therapeutic effect of PRP15 in rat gouty arthritis induced by monosodium urate (MSU) crystals. In the present study, we found that treatment with RPP15 (0.4, 0.8, and 1.2 g/kg) in rats with gouty arthritis induced by MSU crystals significantly attenuated the knee swelling. Histomorphometric and immunohistochemistry analyses revealed that MSU-induced inflammatory cell infiltration and the elevated expressions of nuclear transcription factor-κB p65 (NF-κB p65) in synovial tissues were significantly inhibited, and enzyme-linked immunosorbent assay (ELISA) result showed that MSU-induced high levels of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß), and interleukin-8 (IL-8) in synovial fluid were reduced by treatment with RPP15 (0.4, 0.8, and 1.2 g/kg). We conclude that RPP15 may be a promising candidate for the development of a new treatment for gout and its activity of antigout may be partially related to inhibiting TNF-α, IL-1ß, IL-8, and NF-κB p65 expression in the synovial tissues.

Ethyl acetate extract of Chinese medicinal herb Sarcandra glabra induces growth inhibition on human leukemic HL-60 cells, associated with cell cycle arrest and up-regulation of pro-apoptotic Bax/Bcl-2 ratio.

Sarcandra glabra (Thunb.) Nakai, colloquially known as Caoshanhu, is a Chinese medicinal herb with reported anti-tumor, anti-inflammatory, anti-viral and non-specific immunoenhancing properties. Although the plant has been clinically used for treating a variety of diseases, its bioactive ingredients are largely unknown and its mode of action has never been investigated. In this study, the anti-tumor property of ethyl acetate (EA) extract of S. glabra was investigated by determining its in vitro growth-inhibitory effects on a panel of human cancer cell lines of different histotypes. Growth inhibition of the EA extract on the cancer cells seemed to be selective, and the leukemic HL-60 was found to be the most responsive after 48 h of treatment (IC50=58 microg/ml). Flow cytometric studies further illustrated that the extract might interfere with DNA replication and thus arrested the cell cycle at S phase in the leukemic cells, followed by DNA fragmentation and loss of phospholipid asymmetry in the plasma membrane after 72 h of treatment. Concurrently, the pro-apoptotic Bax/Bcl-2 ratio was also up-regulated by more than 178% of the control level. All these findings suggested that the extract had initiated apoptosis to kill the leukemic cells. Results from this pioneer study help to establish a scientific foundation for future research and development of the bioactive ingredients in EA extract of S. glabra as efficacious anti-cancer agents.

Local anesthesia for functional endoscopic sinus surgery employing small volumes of epinephrine-containing solutions of lidocaine produces profound hypotension.

BACKGROUND: Local anesthetic containing epinephrine is commonly used in many operations for the main purpose of hemostasis. A randomized, controlled, prospective clinical trial was designed to find out hemodynamic changes after local infiltration of different concentrations and/or different dosages of epinephrine during functional endoscopic sinus surgery (FESS) under general anesthesia. METHODS: One hundred and eight adult patients undergoing elective FESS under general anesthesia were randomly allocated into four groups. Group I received 2% lidocaine 2 ml with epinephrine (5 microg/ml); group II received 1% lidocaine 4 ml with epinephrine (2.5 microg/ml); group III received 1% lidocaine 4 ml with epinephrine (5 microg/ml); and group IV received 1% lidocaine 4 ml for local infiltration. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) were monitored continuously in the radial artery and recorded in 6 min: before infiltration (baseline), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, and 6 min after local infiltration. The lowest blood pressure (BP) in this period was also recorded. RESULTS: Significant hemodynamic changes, particularly a decrease in BP (P < 0.001) with a slight increase in HR (P < 0.001) at approximately 1.5 min and an increase in SBP at approximately 3 min (P < 0.01) after local infiltration, were observed in group I, group II and group III compared with the baseline, but not in group IV. No significant hemodynamic differences were observed between group I, group II and group III at the same time points (P > 0.05). CONCLUSION: Local infiltration of low-dose epinephrine causes temporary significant hemodynamic changes particularly a marked decrease in BP during FESS under general anesthesia.

Interrelationship between methionine and cystine of early Peking ducklings.

A 4 x 5 factorial experiment containing 4 cystine levels (0.325, 0.406, 0.487, or 0.568%) and 5 methionine levels (0.285, 0.385, 0.485, 0.585, or 0.685%) was conducted to evaluate the interrelationship between methionine and cystine in corn-peanut meal diet for Peking ducklings from hatch to 21 d of age. Eight hundred 1-d-old male white Peking ducklings were assigned to 20 experimental treatments. All treatments were replicated 4 times using 10 ducklings per pen. As dietary methionine level increased, weight gain and feed intake increased and then decreased; the quadratic response of weight gain was significant (P < 0.05). The methionine requirement for maximum efficiency of feed utilization (0.585%) was higher than for maximum weight gain (0.485%). According to the quadratic model, the optimal methionine requirement of Peking ducklings from hatch to 21 d of age was 0.481% (95% of the level at maximum response). The plasma uric acid concentration was very low (P < 0.05) when dietary methionine was 0.485%. When dietary methionine was excessive (0.685%), the plasma homocysteine concentration increased (P < 0.05). On the other hand, the cystine requirement of ducklings from hatch to 21 d of age was not more than 0.325%. A high level of cystine (0.568%) depressed weight gain and feed intake (P < 0.05), but cystine supplementation in the diets lowered the plasma homocysteine concentration (P < 0.05). There were no significant interactions between methionine and cystine on growth performance, plasma uric acid, and plasma homocysteine.

Functional gamma-secretase inhibitors reduce beta-amyloid peptide levels in brain.

Converging lines of evidence implicate the beta-amyloid peptide (Ass) as causative in Alzheimer's disease. We describe a novel class of compounds that reduce A beta production by functionally inhibiting gamma-secretase, the activity responsible for the carboxy-terminal cleavage required for A beta production. These molecules are active in both 293 HEK cells and neuronal cultures, and exert their effect upon A beta production without affecting protein secretion, most notably in the secreted forms of the amyloid precursor protein (APP). Oral administration of one of these compounds, N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester, to mice transgenic for human APP(V717F) reduces brain levels of Ass in a dose-dependent manner within 3 h. These studies represent the first demonstration of a reduction of brain A beta in vivo. Development of such novel functional gamma-secretase inhibitors will enable a clinical examination of the A beta hypothesis that Ass peptide drives the neuropathology observed in Alzheimer's disease.

Enhancement of erythropoiesis by recombinant human erythropoietin in low birth weight infants: a pilot study.

We randomly assigned eight concurrently symptom-free premature infants (birth weight less than or equal to 1250 gm) at high risk of requiring erythrocyte transfusions for anemia of prematurity to 6 weeks of intensive treatment with either subcutaneous recombinant human erythropoietin (r-HuEPO group) or a placebo (control group). Treatment with r-HuEPO was initiated at a dose of 100 units/kg per day 5 days a week, and was increased to 200 units/kg per day after 2 or 3 weeks if target reticulocyte counts were not achieved. All patients were given supplemental oral iron therapy at a dose of 6 mg/kg per day, as tolerated. Mean reticulocyte counts in r-HuEPO-treated and control infants were 64,600 versus 67,500 cells/mm3 at entry; were 245,600 versus 78,000 cells/mm3 after 1 week; and averaged 262,600 versus 136,400 cells/mm3 during the study. Mean reticulocyte counts in r-HuEPO-treated infants were 251,200 cells/mm3 during the week when r-HuEPO, 100 units/kg per day, was given, and were 269,500 cells/mm3 after the dose was increased to 200 units/kg per day. Mean hematocrit values at entry were 33.4% in babies who received r-HuEPO versus 33.6% in the control subjects, and were 31.4% in r-HuEPO-treated and 25.2% in the control subjects at the end of treatment. One r-HuEPO-treated and three control babies received transfusions during the study; the total volume of blood given was 17 ml in the r-HuEPO group and 101 ml in the control subjects. The percentage of hemoglobin F increased in infants not given transfusions. We conclude that r-HuEPO stimulates endogenous erythropoiesis in small premature babies who are receiving supplemental oral iron therapy. A controlled multicenter trial has been undertaken to confirm these promising preliminary observations.

The preventive effect of radix Salciae miltiorrhizae on monocrotaline-induced pulmonary hypertension in rats.

The preventive effect of Radix Salciae Miltiorrhizae (RSM) on pulmonary hypertension (PHT) and right ventricular hypertrophy (RVH) induced by monocrotaline (MCT) in rats was observed with the methods of measuring the right ventricular systolic pressure (PVSP), the ratio of the right ventricle to the left ventricle plus interventricular septum RV/(LV+S) and the pulmonary small artery morphological analysis. The results show that RSM can reduce the PHT, and prevent the RVH and the increase of the medial thickness of pulmonary small arteries. It can also prevent the endothelial cell injury produced by MCT. The pharmacological effects of RSM on pulmonary circulation were also discussed.

Intramural pericyte degeneration in early diabetic retinopathy study in vitro.

An experimental model of diseased pericytes was established by using cultured bovine retinal capillary pericytes in high--glucose medium. The high glucose stimulated polyol pathway, reduced cellular myo-inositol content and disturbed inositol phospholipid metabolism which resulted in a decrease in inositol trisphosphate (IP3) level. The correlation of suppressed IP3 levels with reduced DNA synthesis was evident. These findings suggested the biochemical mechanism by which retinal pericytes degenerate in high glucose. To supplement myo--inositol and/or an aldose reductase inhibitor to the high--glucose medium largely reversed the suppressed IP3 level and the decreased DNA synthesis. Therefore, these two manipulations may be considered as in vitro therapy to treat sick pericytes induced by high glucose.

Attenuation of phosphoinositidase activity and phosphatidylinositol bisphosphate level of bovine retinal capillary pericytes in high glucose.

Both phosphoinositidase (PIase) and individual species of inositol phospholipid (IPL) of bovine retinal capillary pericytes (BRCP) were quantitatively determined. When glucose in growth medium was increased from 5- to 15- or 30 mM, PIase activity was attenuated to 82% or 55%, respectively. In contrast, when glucose (5-, 15-, 30 mM) was added to an enzyme extract from cells grown in the standard growth medium (5 mM glucose, 0.04 mM myo-inositol) the PIase activity was not changed, indicating that the reduced PIase activity was not due to the direct effect of glucose. When IPLs from BRCP were analysed by HPLC and TLC, we observed reduction of the total and newly formed IPLs including the substrate of PIase. Phosphatidylinositol bisphosphate (PIP2). Reduced levels of IPLs were associated with a decrease in myo-inositol and an increase in sorbitol. The changes in IPL metabolism were reversed by adding either free myo-inositol or AL1576, an aldose reductase inhibitor (ARI), to the high-glucose medium. However, the addition of myo-inositol to the growth medium with a standard concentration of glucose only caused a marked increase in phosphatidylinositol, but not in PIP or PIP2, while the supplement of AL1576 in the standard medium did not cause any changes in IPL formation. These findings suggest that the alteration in IPL metabolism in BRCP may be related to insufficient myo-inositol or activated sorbitol pathway under high-glucose conditions. Further explanation of the role of the altered hydrolysis of PIP2 triggered by PIase may provide clues to understanding of the mechanism of decreased pericyte viability in the presence of high glucose concentrations.