Bacterial antibiotic resistance among cancer inpatients in China: 2016-20.

BACKGROUND: The incidence of infections among cancer patients is as high as 23.2-33.2% in China. However, the lack of information and data on the number of antibiotics used by cancer patients is an obstacle to implementing antibiotic management plans. AIM: This study aimed to investigate bacterial infections and antibiotic resistance in Chinese cancer patients to provide a reference for the rational use of antibiotics. DESIGN: This was a 5-year retrospective study on the antibiotic resistance of cancer patients. METHODS: In this 5-year surveillance study, we collected bacterial and antibiotic resistance data from 20 provincial cancer diagnosis and treatment centers and three specialized cancer hospitals in China. We analyzed the resistance of common bacteria to antibiotics, compared to common clinical drug-resistant bacteria, evaluated the evolution of critical drug-resistant bacteria and conducted data analysis. FINDINGS: Between 2016 and 2020, 216 219 bacterial strains were clinically isolated. The resistance trend of Escherichia coli and Klebsiella pneumoniae to amikacin, ciprofloxacin, cefotaxime, piperacillin/tazobactam and imipenem was relatively stable and did not significantly increase over time. The resistance of Pseudomonas aeruginosa strains to all antibiotics tested, including imipenem and meropenem, decreased over time. In contrast, the resistance of Acinetobacter baumannii strains to carbapenems increased from 4.7% to 14.7%. Methicillin-resistant Staphylococcus aureus (MRSA) significantly decreased from 65.2% in 2016 to 48.9% in 2020. CONCLUSIONS: The bacterial prevalence and antibiotic resistance rates of E. coli, K. pneumoniae, P. aeruginosa, A. baumannii, S. aureus and MRSA were significantly lower than the national average.

[MicroRNA-1249 regulates the apoptosis of myocardial cells in rats with chronic intermittent hypoxia by autophagy].

Objective: To investigate the regulation and possible mechanism of microRNA (miR)-1249 on myocardial apoptosis in chronic intermittent hypoxia rats. Methods: A total of 16male SD rats aged 8 weeks were randomly divided into 2 groups by the random number table: normoxia control group and chronic intermittent hypoxia group (CIH) (n=8 each). The CIH group was exposed to intermittent hypoxia every day from 9: 00 to 17: 00 for 8 consecutive weeks, while the control group received the same frequency of pulse air. Hemodynamic values were measured via a cannula inserted into right common carotid artery. The expressions of miR-1249 and microtubule-associated protein light chain 3 (LC3) mRNA were observed by real-time PCR. The expressions of LC3 and Cleaved Caspase-3 were detected by Western bolt. TUNEL staining was performed to detect myocardial apoptosis. The rat cardiomyocyte cell H9C2 was divided into normoxia group, intermittent hypoxia (IH) group and miR-1249 inhibitor transfected and IH treatment group (inhibitor group). At the end of the experiment, the activation of LC3 protein in each group of cells was determined. Results: Compared with normoxia control group, left ventricle end diastolic pressure (LVEDP) increased [(4.6±0.4) vs (2.2±0.1) mmHg (1 mmHg=0.133 kPa)], left ventricular systolic pressure (LVSP) , maximal rate of pressure decline (-dp/dtmax), and maximal rate of pressure development (+ dp/dtmax) decreased in CIH group [(92.7±4.1) vs (135.3±3.2) mmHg, (4 247±108) vs (7 626±235) mmHg/s, and (3 168±105) vs (6 028±81) mmHg/s] (all P<0.001). The expression of miR-1249 and LC3 mRNA were significantly higher in CIH group than that in normoxia control group (all P<0.001), and a positive correlation was found between the expression of LC3 mRNA and miR-1249. The expression of LC3 and Cleaved Caspase-3 protein in myocardial tissue of CIH rats were significantly higher than that of the normoxia control group (all P<0.001). The proportion of myocardial cell apoptosis in CIH rats was significantly higher than that in the normoxia control group [(23.84±4.94)% vs (2.93±0.73)%] (P<0.001). The activation of LC3 in myocardial cells of inhibitor group was significantly lower than that of IH group, but higher than that in normoxia group. Conclusions: CIH could induce LC3 by raising the expression of miR-1249, and then induce the activation of apoptosis protein Caspase3. It ultimately induces myocardial apoptosis.

[Clinicopathologic features with collecting duct carcinoma of kidney: report of 10 cases].

Objective: To study the pathological features, immunophenotypes, differential diagnoses and prognostic parameters of collecting duct carcinoma of the kidney (CDC). Methods: Clinical imaging, histopathology, immunohistochemistry, and survival data of 10 patients at First Affiliated Hospital of Nanjing Medical University from January 2009 to August 2017 were retrospectively analyzed along with a review of literatures. Results: The clinical symptoms of CDC were not specific, and image examinations showed space-occupying mass lesions. Tumors were mainly located in renal medulla with grey and firm cut face and the presence of focal hemorrhage and necrosis. Microscopically, there were predominant tubular or tubular-papillary structures with associated focal sarcomatoid areas, desmoplastic stromal reaction and lymphoplasmacytic cells infiltration. Tumor cells had marked cytological atypia with high grade nuclei, conspicuous nucleolus and numerous mitoses. Immunohistochemically, tumor cells were strongly positive for CK19, E-cadherin, vimentin, HCK, CK7 and PAX8. The main treatment was radical nephrectomy in the patients. Seven cases died of CDC with median survival of 10 months. Conclusions: CDC is a rare, highly aggressive malignancy of kidney with poor prognosis. Definitive diagnosis should be made by histology and immunohistochemistry. Differential diagnoses include papillary renal cell carcinoma(type Ⅱ), renal medullary carcinoma, infiltrating high grade urothelial carcinoma, renal pelvis adenocarcinoma and metastatic adenocarcinomas.

[Effects of Prescription Yiqi Huatan Quyu on oxidative stress level and pathological changes in chronic intermittent hypoxia rat liver].

Objective: To investigate the effects of Yiqi Huatan Quyu prescription on oxidative stress and pathological changes in chronic intermittent hypoxia rats liver. Methods: A total of 24 male SD rats aged eight weeks were randomly divided into 3 groups by the random number table: normal control group (NC), chronic intermittent hypoxia group (CIH) and chronic intermittent hypoxia plus Yiqi Huatan Quyu prescription supplement group (Chinese medicine group, CM)(n=8 each). The CIH group and CIHN group were exposed to intermittent hypoxia every day for 8 consecutive weeks. In addition, the CIHN group received Yiqi Huatan Quyu prescription via gavage 30 min before the CIH. Eight weeks later, serums were collected to test alanine aminotransferase (ALT) and aspartate aminotransferase (AST) level. Meanwhile, rat livers were extracted to evaluate malondialdehyde (MDA), total superoxide dismutase (T-SOD), glutathione (GSH) and Nuclear factor κB (NF-κB) and observe the pathological changes of liver. Results: The levels of serum ALT and AST in the CIH group were significantly higher than those of NC group[(112.1±31.7) vs (41.3±6.6) U/L, (295.4±39.8) vs (104.5±12.3) U/L], the contents of the MDA and NF-κB in the CIH group were notably higher than those of NC group[(7.9±1.1) vs (3.6±0.7) nmol/mgprot, (16.2±3.3) vs (5.7±2.2) ng/L], the activities of T-SOD and GSH in the CIH group were significantly lower than those of control group[(181.6±28.6) vs (304.3±42.9) U/mgprot, (5.5±1.3) vs (14.9±2.4) mg/gprot](all P<0.001). The levels of the serum ALT and AST in CM group were significantly lower than those of CIH group[(52.2±8.6) vs (112.1±31.7) U/L, (148.1±20.4) vs (295.4±39.8) U/L], the contents of liver MDA in CM group was notably lower than those of CIH group[(4.5±0.7) vs (7.9±1.1) nmol/mgprot], the activities of liver T-SOD and GSH in CM group were significantly higher than those of CIH group[(226.9±38.9) vs (181.6±28.6) U/mgprot, (10.3±1.7) vs (5.5±1.3) mg/gprot](all P<0.05). Compared with CIH group, declining tendency was observed from contents of NF-κB in CM group, but there was no statistical difference[(15.8±2.1) vs (16.2±3.3) ng/L, P>0.05]. Pathology observation showed the CIH group had abundant inflammatory cells infiltration in the liver portal area and the inflammatory cells infiltration decreased following Chinese medicine treatments. Conclusion: Yiqi Huatan Quyu prescription has some protection to CIH rat liver, which might mediate by the reduction of oxidative stress and inflammatory mediator.

Activation of extracellular signal-regulated kinase by TGF-beta1 via TbetaRII and Smad7 dependent mechanisms in human bronchial epithelial BEP2D cells.

Transforming growth factor-beta1 (TGF-beta1) can activate mitogen-activated protein kinases (MAPKs) in many types of cells. The mechanism of this activation is not well elucidated. Here, we explore the role of TGF-beta/Smads signaling compounds in TGF-beta1-mediated activation of extracellular signal-regulated kinase (ERK) MAPK in human papillomavirus (HPV)-18 immortalized human bronchial epithelial cell line BEP2D and the role of TGF-beta1-induced phosphorylation of ERK in proliferation and apoptosis of BEP2D. The cell models of siRNA-mediated silencing of TGF-beta receptor type II (TbetaRII), Smad2, Smad3, Smad4, and Smad7 were employed in this study. Our results demonstrate that TGF-beta1 activates ERK in a time-dependent manner with a maximum effect at 60 min; overexpression of Smad7 increased this TGF-beta1-mediated phosphorylation of the ERK; and siRNA-mediated silencing of TbetaRII, Smad3, Smad4, and Smad7 abrogated this effect. Moreover, we observed that overexpression of Smad7 restored TGF-beta1-mediated ERK phosphorylation in Smad4 knockdown cells but not in TbetaRII knockdown cells. In BEP2D cells, TGF-beta1 treatment effectively inhibited cells' proliferation and induced their apoptosis. Pretreatment with U0126, an inhibitor of ERK1/2, significantly enhanced the TGF-beta1-mediated antiproliferative and apoptosis induction effects in BEP2D cells. These data revealed that TbetaRII and Smad7 play the critical roles in TGF-beta1-mediated activation of ERK; Smad3 and Smad4 can play an indirect role through up-regulating Smad7 expression; and TGF-beta1-induced phosphorylation of ERK may participate in BEP2D cell proliferation and apoptosis regulation.

[Methodological studies on quantitative determination of beta-eudesmol in Atractylodes lancea (thunb.) DC].

OBJECTIVE: To establish methodologically a method for quantitative determination of beta-eudesmol in Atractylodes lancea. METHOD: GC, column: 3 mm x 2 m; stationary phase; 15% QF-1; support: Chromosorb WAW(60-80 mesh); detector: hydrogen flame ionization detector; injection chamber temperature: 210 degrees C; column temperature: 174 degrees C; carrier gas: N2:50 ml.min-1, air: 49 kPa, H2:58.8 kPa; sensibility range: 10(2) x 64; chart speed: 2.5 mm.min-1. RESULT: Average recovery ratio is 100.7% (n = 5). CONCLUSION: This method can be used to control the quality of A. lancea.

Effects of 17beta-estradiol on the baroreflex control of sympathetic activity in conscious ovariectomized rats.

The effects of chronic treatment with 17beta-estradiol on baroreflex control of sympathetic activity were examined in conscious unrestrained ovariectomized rats. Baroreflex function was evaluated by logistic sigmoidal analysis of the relationships between changes in mean arterial pressure (MABP) and changes in heart rate (HR) and splanchnic nerve activity (SNA) when MABP was rapidly increased to 150 mmHg by intravenous phenylephrine after its reduction to 50 mmHg by intravenous nitroprusside. These baroreflex function curves were similar in vehicle- and estradiol-treated rats. However, after a 30-min infusion of vasopressin in vehicle-treated rats, the curve for HR was shifted downward, and the upper plateau and maximum gain for the SNA curve were reduced. These effects were abolished by estradiol. A 30-min phenylephrine infusion had no effect on the baroreflex curves. Thus estrogen can modulate the action of vasopressin on baroreflex control of sympathetic outflow and thereby participate in cardiovascular regulation.

Effects of 17beta-estradiol on sympathetic activity and pressor response to phenylephrine in ovariectomized rats.

The effects of 17beta-estradiol (E2) on sympathetic activity were examined in conscious unrestrained ovariectomized rats, instrumented under methohexital anesthesia to record mean arterial pressure (MABP), heart rate (HR), renal nerve activity (RNA), and splanchnic nerve activity (SNA) 1 day before the experiment. Injection of E2 (150 micrograms/kg iv) caused reductions (P < 0.01) in RNA (29 +/- 6%), SNA (25 +/- 2%), and HR (26 +/- 5 beats/min) within 20 min, but MABP remained unchanged. Ninety minutes after intravenous injection of E2 or vehicle, intravenous infusion of phenylephrine (PE; 6.2 micrograms . min-1 . kg-1) induced similar increases in MABP and decreases in HR, RNA, and SNA in both groups. By contrast, in rats chronically treated with E2, the pressor response to PE was smaller (P < 0.01; 22 +/- 5 mmHg) than in vehicle-treated rats (40 +/- 4 mmHg). The changes in HR, RNA, and SNA were similar in both groups, but the ratios of changes in HR and SNA to MABP, an index of baroreflex sensitivity, were greater in the E2-treated rats. These findings suggest that E2 can act centrally to modulate sympathetic function and thereby participate in cardiovascular regulation.

Long-term increases in renal sympathetic nerve activity and hypertension.

1. Essential hypertensive patients have been characterized by increased sympathetic nerve activity, increased peripheral vascular tone, decreased plasma volume and normal cardiac output when compared with normotensive subjects. Bilateral renal denervation reduces the magnitude or delays the onset of the blood pressure response in numerous models of experimental hypertension regardless of the aetiology of the elevation in arterial pressure. 2. Using a servocontrolled intrarenal infusion system, we have elevated intrarenal noradrenaline concentration via intermittent renal artery infusion without decreasing renal blood flow as a method of simulating selective elevation of renal sympathetic outflow. 3. Chronic intrarenal adrenergic stimulation increased arterial pressure within 24 h and this hypertension persisted for 28 consecutive days. The elevated arterial pressure was not associated with sustained increases in plasma renin activity, aldosterone, circulating catecholamines, arginine vasopressin or significant renal vasoconstriction. Urinary sodium excretion was chronically elevated and the dogs remained in negative sodium balance for the duration of the intrarenal noradrenaline infusion. 4. After 2 weeks of elevated intrarenal neurotransmitter coupled with hypertension, renal vascular reactivity to further adrenergic stimulation was significantly increased because the hypertension was maintained during continual reductions in the daily dosage of neurotransmitter allowed to be infused by the servocontroller. After only 28 days of noradrenaline infusion, renal vascular hypertrophy developed in vessels from 150-300 microns. 5. We conclude that selective and intermittent increases in intrarenal adrenergic neurotransmitter are sufficient to elicit chronic hypertension in the absence of volume expansion. This intrarenal neuroadrenergic hypertension is closely associated with the haemodynamic parameters which characterize a major subset of human essential hypertensives.

Effects of furosemide and verapamil on the NaCl dependency of macula densa-mediated renin secretion.

The present studies in perfused specimens of the juxtaglomerular apparatus microdissected from rabbit kidneys were performed to quantitatively evaluate the relation between macula densa NaCl concentration and renin secretion and to study the effect of furosemide and verapamil on NaCl dependency of renin release. Renin secretion was found to decrease exponentially when macula densa NaCl concentration was increased from 26/7 mmol/L (Na/Cl) to 46/27, 66/47, and 86/67 mmol/L. Increasing Na/Cl concentrations from 86/67 to 106/87 mmol/L had no further effect on renin secretion. [Cl]1/2, the chloride concentration producing the half-maximal effect, was 30 mmol/L. Addition of 50 mumol/L furosemide to the luminal fluid caused renin secretion to become essentially independent of macula densa NaCl concentration. This effect was due to both an increase of renin secretion at high NaCl concentrations and a decrease of renin release at low NaCl concentrations. Verapamil added to the superfusate at a concentration of 1 mumol/L also abolished NaCl dependency of renin secretion; most of this effect was due to an increase of renin release at high luminal NaCl. These results suggest that Na-2Cl-K cotransport and calcium flux through voltage-gated channels are two mechanisms required for the expression of NaCl-dependent renin release. Identification of the cellular localizations of these two critical membrane proteins in the renin control pathway requires further study.

Effect of nitric oxide on renin secretion. I. Studies in isolated juxtaglomerular granular cells.

Experiments were performed on juxtaglomerular granular cells (JGC) in short-term primary culture to determine the direct immediate effect of NO on renin secretion and to test whether JGC are able to generate NO. Renin secretion was measured repeatedly over short time intervals in a cell superfusion system. Renin release did not significantly decrease over a 40-min observation period in untreated JGC. Addition of sodium nitroprusside (SNP) caused a reduction in renin release (measured in nano-Goldblatt hog units vs. time, i.e., nGU/min) from 479 +/- 25, 423 +/- 70, and 388 +/- 54 nGU/min to 295 +/- 19 (n = 5), 102 +/- 21 (n = 7), and 71 +/- 9 nGU/min (n = 6) with 10(-5), 10(-4), and 10(-3) M SNP, respectively. In the presence of the guanylate cyclase inhibitor methylene blue at 10(-4) M, SNP at 10(-4) M had no significant effect on renin secretion. 8-Bromoguanosine 3',5'-cyclic monophosphate at 10(-4) M in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (10(-3) M) caused a reduction of renin secretion to 50.1 +/- 3.6% of control. To examine the possibility that renin secretion is affected by NO release from JGC, we assessed the effect of the NO synthase (NOS) substrate L-arginine (10(-3) M) and the NOS blocker N omega-nitro-L-arginine (10(-4) M) on renin secretion. Renin release was not significantly altered by either stimulation or inhibition of NOS activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of nitric oxide on renin secretion. II. Studies in the perfused juxtaglomerular apparatus.

To examine the possible role of NO in macula densa control of renin secretion, we examined the effects of varying NO availability on renin release in the isolated perfused rabbit juxtaglomerular apparatus (JGA). Gradual increments of luminal Na/Cl concentration ratio (mM/mM) from 26/7 over 46/27, 66/47, to 86/67 caused a progressive decrease in renin secretion from (as log of nano-Goldblatt hog units vs. time, i.e., log nGU/min) 1.09 +/- 0.34 to 0.46 +/- 0.24 log nGU/min, with the greatest change occurring at the first concentration step. The presence of 0.7 mM N omega-nitro-L-arginine (NNA), an NO synthase inhibitor, in the luminal fluid significantly reduced renin secretion at the lowest Na/Cl concentration ratio to 0.65 +/- 0.32 log nGU/min (P < 0.01 compared with control). Renin secretion at the higher Na/Cl concentration ratios was not significantly affected by NNA compared with control. In contrast to these results, the addition of the NO donor nitroprusside (1 mM) to the bath caused a reduction in renin secretion from 1.0 +/- 0.39 to 0.47 +/- 0.46 log nGU/min (P < 0.05), an effect that was reversed by bath addition of 0.01 mM methylene blue. Similarly, addition of L-arginine (0.7 mM) to the bath reduced renin secretion from 0.99 +/- 0.37 to 0.81 +/- 0.38 log nGU/min (P < 0.01), whereas addition of L-arginine to the luminal fluid increased renin secretion from 0.85 +/- 0.43 to 1.94 +/- 0.46 log nGU/min (P < 0.05). The stimulatory effect of luminal L-arginine was reversed by the luminal addition of NNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Renin and renin mRNA in proximal tubules of the rat kidney.

The present study was undertaken to assess the presence of renin enzymatic activity and renin mRNA in proximal tubules of rat kidneys, and to determine the effect of converting enzyme inhibition (CEI) on proximal tubule renin gene expression. Proximal convoluted tubules (PCT), proximal straight tubules (PST), outer medullary collecting ducts (OMCD), and glomeruli (Gloms) were isolated by microdissection. Renin activity was measured in sonicated segments by radioimmunoassay. Renin mRNA levels were assessed using a quantitative PCR. Renin activity in PCT averaged 51 +/- 15 microGU/mm compared to 405 +/- 120 microGU/glomerulus. No measurable renin activity was found in PST and OMCD. Renin activity in both glomeruli and tubules had the same pH optimum, between 7.0 and 7.5. Renin mRNA was consistently detectable in cDNA prepared from PCT and PST, although its abundance per mm tubule was about 1/500th that found in one glomerulus. Renin mRNA was not detectable in OMCD. Tubular renin PCR product identity was confirmed by restriction digestion. CEI administration increased glomerular renin activity and renin mRNA, but not proximal tubular renin. The absence of a stimulatory effect of CEI on proximal tubule renin gene expression suggests the operation of different intracellular signals in control of renin synthesis in the proximal tubule than in the vascular compartment.

Effect of prostaglandin synthesis inhibition on macula densa-stimulated renin secretion.

The purpose of the present studies was to evaluate directly the role of prostaglandins in macula densa-mediated renin release. Individual juxtaglomerular apparatus specimens were microdissected from rabbit kidney and perfused with a solution containing either high NaCl (Na+ = 141 meq/l; Cl- = 122 meq/l) or low NaCl (Na+ = 26 meq/l; Cl- = 7 meq/l) concentration. With a step decrease in perfusate NaCl (high to low), renin secretion rate was markedly stimulated (from 15.06 to 63.1 nGU/min, P < 0.01), and the response was almost fully reversible. When specimens were bathed with cyclooxygenase inhibitors flurbiprofen (10(-5) M) or flufenamic acid (10(-4) M), this macula densa-activated increase in renin release was largely or completely abolished (flurbiprofen, 3.5-10.5 nGU/min, not significant; flufenamic acid, 9.0-12.3 nGU/min, not significant). Exposing the macula densa to a step increase in perfusate NaCl concentration (low to high) resulted in a significant and reversible suppression of renin secretion in control specimens, but no significant suppression was seen in specimens treated with flufenamic acid. These data provide direct evidence to support the hypothesis that locally produced prostaglandins may act as a primary mediator of the renin response to macula densa activation.

Effects of adenosine and angiotensin on macula densa-stimulated renin secretion.

The present studies were performed to assess, in the isolated perfused juxtaglomerular apparatus of the rabbit kidney, the effect of exogenous adenosine on renin secretion stimulated by a low NaCl concentration at the macula densa. Addition of adenosine to the bath resulted in a change of renin secretion from 30.4 to 23.9 nGU/min at an adenosine concentration of 10(-6) M (n = 7; P = NS), from 38.6 to 17.9 nGU/min at a concentration of 10(-4) M (n = 7; P = 0.038), and from 18.4 to 5.8 nGU/min at 10(-2) M (P = 0.0053). Addition of the A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine at 10(-5) M fully reversed the effect of adenosine at 10(-4) M, but not at 10(-2) M. Inhibition of adenosine breakdown by the adenosine deaminase inhibitor pentostatin (10(-6) M) enhanced the inhibitory effect of adenosine with renin secretion falling from 61.7 to 19.5 nGU/min at 10(-6) M adenosine (P = 0.035) and from 44.7 to 13.5 nGU/min at 10(-4) M adenosine (n = 0.027). A marked inhibition of NaCl-dependent renin secretion was caused by both angiotensin II (P = 0.011) and angiotensin III (P = 0.006), both at 10(-8) M. These results show that adenosine is capable of reducing macula densa-mediated renin secretion, but that this effect, even at very high concentrations or during adenosine deaminase blockade, does not fully mimic the inhibitory potency of increasing luminal NaCl concentration. Because the marked effect caused by angiotensins establishes the potential of this preparation to demonstrate inhibitory hormonal influences, it is concluded that adenosine does not appear to be the sole paracrine factor responsible for the NaCl-induced reduction of renin secretion.

[Stimulation of the brain osmoreceptor attenuates the sensitivity of tubuloglomerular feedback in rats].

By using micropuncture technique and measuring inulin concentrations in plasma and tubular fluid, and tubular flow rate, single nephron glomerular filtration rate (SNGFR) was calculated. The effect of stimulation of the brain osmoreceptors on the sensitivity of tubulo-glomerular feedback in rats was observed. The SNGFR value measured at the proximal tubular (SNGFRp) was greater than that measured at the distal tubule (SNGFRd) of the same nephron. The difference between these two values (SNGFRp-d) was a measure of the extent of tubuloglomerular feedback (TGF). The SNGFRp-d value was reduced after intracerebroventricular administration of hypertonic saline (icv. HS), indicating that stimulation of the brain osmoreceptor can attenuate the sensitivity of TGF. The icv. HS-induced increase in renal plasma flow rate and glomerular filtration rate could be abolished by intravenous injection of furosemide, while natriuretic response persisted. These results suggest that icv. HS can alter renal hemodynamics via reduction of TGF, and confirm the claim that icv. HS can inhibit tubular reabsorption, which is responsible for the natriuretic response.

[Role of the hypophysis in the renal responses upon stimulation of the brain osmoreceptor].

The experiments were performed in rats anaesthetized with alpha-chloralose and urethane. Intracerebroventricular administration of hypertonic saline (icv. HS) resulted in an increase in renal plasma flow rate, glomerular filtration rate, urine flow rate, urinary sodium excretion, urinary potassium excretion, and osmolar clearance, and a decrease in free water clearance. These responses were abolished in hypophysectomized rats, but were not significantly affected by intravenous injection of vasopressin (VP) receptor (V1 and V2) antagonist. The urinary dopamine (DA) excretion did not change significantly after icv. HS. Moreover, administration of benserazide, an inhibitor of the enzyme L-aromatic amino acid decarboxylase that converts L-dopa to DA, did not attenuate the diuresis and natriuresis induced by icv. HS. These results suggest that the renal responses upon stimulation of the brain osmoreceptor are dependent on the integrity of the hypophysis, while the VP and DA are not essential to these renal responses. The hypophysial factors responsible for the icv. HS-induced renal responses remain to be explored.

[The effects of stimulation of the brain osmoreceptor on the tubular reabsorption of sodium, chloride and potassium in rats].

The tubular reabsorption of sodium, chloride and potassium was studied with micropuncture technique and electron probe X-ray microanalysis before and following intracerebroventricular administration of hypertonic saline (icv. HS) in rats. At the late proximal convoluted tubules, the fractional delivery of sodium increased from 53.0 +/- 2.1% to 66.0 +/- 2.9% (P < 0.01), the fractional delivery of chloride increased from 65.4 +/- 3.4% to 78.2 +/- 3.9% (P < 0.05), but the fractional delivery of potassium and tubular fluid osmolarity were unaltered. At the early distal convoluted tubules, the fractional delivery of sodium increased from 8.2 +/- 0.9% to 13.6 +/- 1.8% (P < 0.05), the fractional delivery of chloride increased from 5.4 +/- 0.8% to 9.5 +/- 1.4% (P < 0.05), the tubular fluid osmolality increased from 139.8 +/- 6.9 mOsm/kg H2O to 181.3 +/- 15.6 mOsm/kg H2O2 whereas fractional delivery of potassium did not show significant change. Under the condition of diuresis provoked by the intravenous administration of furosemide the kaliuresis induced by icv. HS was abolished, while the icv. HS-elicited diuresis and natriuresis remained unaffected. These results indicate that stimulation of the brain osmoreceptor inhibits the proximal tubular reabsorption of sodium chloride which in turn enhances sodium-potassium exchange in the distal tubules and collecting ducts.

[Effect of brain osmoreceptor stimulation on the function of superficial nephrons in the rat].

Our previous work with lithium clearance method indicated that the diuresis and natriuresis induced by intracerebroventricular administration of hypertonic saline (icv. HS) resulted from an increase in glomerular filtration rate and a decrease in water and sodium reabsorption in the proximal tubules. In the present study, we further observed the effect of icv. HS on the glomerular filtration rate and proximal convoluted tubular and loop reabsorption in the superficial nephrons with micropuncture technique. After icv. HS, single nephron glomerular filtration rate increased from 39.6 +/- 1.9 nl/min to 48.8 +/- 2.0 nl/min (P less than 0.001), late proximal convoluted tubular fluid flow rate increased from 20.5 +/- 1.4 nl/min to 28.4 +/- 2.0 nl/min (P less than 0.01), and the ratio of tubular fluid inulin concentration to plasma inulin concentration decreased from 1.98 +/- 0.08 to 1.69 +/- 0.05 (P less than 0.01). Calculated fractional proximal convoluted tubular fluid reabsorption decreased from 49.2 +/- 2.2% to 41.7 +/- 1.8% (P less than 0.001), while calculated absolute proximal convoluted tubular fluid reabsorption did not change significantly. These results coincided with the observation with lithium clearance method. In addition, icv. HS increased absolute loop fluid reabsorption but decreased fractional loop fluid reabsorption. The present data suggest that stimulation of the brain osmoreceptor increases the glomerular filtration rate and decreases the reabsorption capacity of the proximal convoluted tubule in the superficial nephrons, both these responses result in an increase in the load of the loop of Henle with a secondary change in loop reabsorption. However, the results of the present study do not rule out the possibility that icv. HS may also inhibit the loop reabsorption directly.

[A modified microanthrone method for the determination of inulin on nanogram scale].

The establishment of a method of determining minute amount of inulin on nanogram scale is essential for applying micropuncture technique to kidney research. In this experiment, we modified a classical microanthrone method which was used by Dirks et al. to determine inulin contained in tubular fluid. A spectrophotometer was installed with a special microcuvette to suit the colorimetry of 10 microliters solution. Linear relation between inulin concentration and absorption was observed in the range of inulin concentration from 2 to 32 nl per 10 microliters anthrone reagent. The accuracy of this microanthrone method was evaluated with inulin recovery test, the mean recovery rate being 101.2 +/- 3.5%. Since tubular fluid did not interfere with the determination of inulin, the tubular fluid which contained inulin could be added directly to anthrone reagent in actual practice. The mean single nephron glomerular filtration rate measured with this modified microanthrone method in 21 rats was 34.9 +/- 1.8 nl/min, which coincided well with the values reported in literature. The results indicate that the measurement of inulin with the above-mentioned microanthrone method is reliable and suitable for the micropuncture study.