Hepatic adenine nucleotides and microsomal cholesterol 7 alpha-hydroxylase activity in the obstructed and freely draining lobes of the liver after selective bile duct obstruction

BACKGROUND: The effect of selective bile duct obstruction (SBDO) on hepatic reserve function of the bile duct obstructed (BDO) and nonobstructed freely draining (FD) lobes of the liver is obscure. METHODS: The bile duct branches draining from the left lateral and median lobes of the liver were ligated for 4 and 10 days in rats, and hepatic reserve functions in BDO and FD lobes were assessed by microsomal cholesterol 7 alpha-hydroxylase activities and by hepatic adenine nucleotides and energy charge levels. The values were compared with those in the sham-operated control liver. Cholesterol 7 alpha-hydroxylase activities were determined by gas-liquid chromatography--mass spectrometry, and hepatic adenosine triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP) levels with high-pressure liquid chromatography. RESULTS: The histological examination of the BDO lobes showed proliferation and formation of new bile ductules and fibrous connective tissues linking portal areas. Microsomal cholesterol 7 alpha-hydroxylase activities, hepatic energy charge and each adenine nucleotide level did not differ between FD and BDO lobes, and the values were similar to those in the sham-operated liver. CONCLUSIONS: Selective bile duct obstruction shows no adverse effects on microsomal and mitochondrial functions in both the BDO and FD lobes of the liver.     

Beneficial effects of Tadenan therapy after two weeks of partial obstruction in the rabbit

Tadenan (Debat Laboratories, France) is a plant extract used in Europe for the treatment of micturition disorders associated with benign prostatic hypertrophy (BPH). Prior studies demonstrated that pretreatment of rabbits with Tadenan significantly reduced the contractile dysfunction observed after 2 weeks of partial outlet obstruction. The specific aim of the present study was to determine the effect of Tadenan therapy following the creation of partial outlet obstruction. Two sets of experiments were performed: one with mild and the other with severe outlet obstruction. For both sets of experiments, male New Zealand rabbits (3-5 kg) were separated into 3 groups of 5 rabbits each. Each rabbit in groups 1 and 2 was obstructed using standard methodology. Rabbits in group 3 served as controls and did not receive any surgery. After 2 weeks, each rabbit in group 1 received Tadenan orally at 100 mg/kg/day for 3 weeks; each rabbit in group 2 received vehicle (peanut oil). After 3 weeks of treatment (5 weeks after partial outlet obstruction), rabbits were anesthetized and cystometries were performed. Immediately after cystometry, the rabbits were euthanized, the bladder rapidly removed, and 4 longitudinal strips prepared and mounted in individual baths for contractile studies. The contractile responses to field stimulation, carbachol, adenosine-5'-triphosphate (ATP), and potassium chloride (KCl) were determined, as follows: (1) Bladder mass approximately doubled in the mildly obstructed groups. Bladder mass increased significantly (3-5-fold) in the severely obstructed groups. (2) Cystometrograms from the mildly obstructed rabbits treated with peanut oil showed low compliance, whereas those of the mildly obstructed rabbits treated with Tadenan showed normal compliance. The cystometrograms of all severely obstructed rabbits showed low compliance. (3) Mild obstruction caused small but significant decreases in the contractile response to field stimulation that were reversed by Tadenan treatment. No changes were noted in response to bethanechol, ATP, and KCl stimulation. (4) Severe obstruction caused significant decreases in the response of bladder strips to field stimulation and bethanechol. Following Tadenan therapy, there was a significant improvement in the response to high-frequency field stimulation and a substantial improvement in the response to bethanechol (response equal to control). No changes were noted in response to ATP and KCl stimulation. In conclusion, Tadenan treatment reversed the bladder dysfunctions induced by mild partial outlet obstruction, and resulted in improved bladder function in the severe model of outlet obstruction. These studies are consistent with previous studies showing that Tadenan pretreatment protects the bladder against the development of contractile dysfunctions.     

Effect of neonatal surfactant therapy on lung function at school age in children born very preterm

BACKGROUND: Involuntary detrusor contractions often cause irritative symptoms such as urgency and incontinence. A dog model for acutely induced variable bladder outlet resistance was developed to investigate the possible role of prostatic afferent nerve fibers in the development and maintenance of detrusor instability. METHODS: Fifty-eight mongrel dogs (weight range 19.5-36.5 kg) were divided into five groups: group I (n = 11) had surgically induced bladder outlet obstruction. Group II (n = 14) had urinary obstruction and bilateral sectioning of the lowest branches of the pelvic plexus supplying the prostate. Group III (n = 10) had prostate denervation only. Groups IV (n = 10) and V (n = 13) were sham-operated and controls, respectively. In the obstructed groups (I and II), an artificial urinary sphincter (length 4.5-6.0 cm) was placed around the bladder neck and connected to a reservoir placed subcutaneously to allow postoperative adjustments of urinary resistance. All dogs were evaluated at baseline and postoperatively at 1, 3, and 6 months with uroflowmetry, postvoid residual urine volume, cystometry as well as serum creatinine, and urinalysis. RESULTS: Occurrences of detrusor instability were not associated with prostatic denervation input. The mean peak flow rates decreased significantly in the obstructed groups at all follow-ups, but did not change significantly in the nonobstructed groups. Postoperatively, the mean maximum bladder capacity was significantly decreased for groups I and II only. However, a significant correlation between maximum bladder capacity and maximum detrusor pressure could not be detected at any time point in any of the groups. Mean postvoid residual urine volume varied considerably in all groups over time. Creation of a urinary model of infravesical obstruction was associated with considerable problems. CONCLUSIONS: In our dog model of bladder outlet obstruction, prostatic sensory nerve fibers appear not to be involved in detrusor instability. Surgical induction of a constant model of bladder outlet obstruction was difficult even in a large animal. The observations from the present study raise questions about the validity of obstructive urinary animal models.     

The lived experience of women military nurses in Vietnam during the Vietnam War

Excitation-contraction coupling is achieved by translocation of calcium from the extracellular space as well as by the release of calcium from intracellular stores. Thapsigargin has been shown to selectively block the sarcoplasmic Ca-ATPase, thereby preventing the reuptake of calcium into intracellular stores and the participation of these calcium storage sites in the contractile response to stimulation. The current study determined the effect of thapsigargin on the contractile response to field stimulation, bethanechol, and KCl in control rabbit bladders and bladders obtained from rabbits subjected to partial outlet obstruction. Partial bladder outlet obstruction resulted in a marked increase in bladder mass and in significant decreases in the contractile response to field stimulation, bethanechol, and KCl. Thapsigargin (5-40 microM) had no effect on the contractile responses of bladder strips isolated from control rabbits to field stimulation, bethanechol, or KCl. However, bladder strips isolated from obstructed rabbits showed a significant concentration-dependent decrease in the contractile response to field stimulation in the presence of thapsigargin. Thapsigargin had no effect on the contractile responses of bladder strips isolated from obstructed rabbits to either bethanechol or KCl. In general, the data described in this study support our current hypothesis: as smooth muscle cells enlarge (hypertrophy) and the cell volume increases, there is an increased dependence on the release of intracellular calcium from the sarcoplasmic reticulum to mediate the contractile response to field stimulation.     

Gas chromatography determination of polychlorinated biphenyls in powdered and liquid soybean milks

OBJECTIVE: To compare the inhibitory effects of propiverine HCl(BUP-4) with those of atropine and oxybutynin on the detrusor instability induced by partial obstruction of the bladder neck of female rats. MATERIALS AND METHODS: Partial obstruction was created using partial ligation of the proximal urethra in 20 female Sprague-Dawley rats. Both the obstructed rats and a control group of 15 rats were evaluated cystometrically about 6 weeks later and the values compared both baseline and after injection with BUP-4, atropine or oxybutynin. During cystometry, the bladder capacity (BC), residual volume (RV), compliance and frequency of spontaneous activity (SA) were determined. RESULTS: The BC, RV and frequency of SA were significantly increased, and compliance markedly decreased, in obstructed compared with normal rats. The micturition pressure was significantly decreased only after injection with BUP-4 in both normal and obstructed rats. For both, the BC was increased significantly after injection with atropine or BUP-4 (P < 0.05), with the increase greater after BUP-4 than after atropine in both groups (P < 0.01). After injecting BUP-4, the RV was significantly increased in both groups (P < 0.05); atropine increased the RV only in normal rats (P < 0.01) and oxybutynin had no significant effect on RV. Increases in compliance after the administration of each drug were significant only in obstructed rats (P < 0.01) and were markedly higher after oxybutynin (780%) than after the other drugs (180-250%). The frequencies and amplitude of SA after injection with each drug were significantly lower only in obstructed rats, but in these rats, there were no significant differences in this reduction after injecting oxybutynin or BUP-4, whereas they were significantly greater after injecting oxybutynin than after atropine. CONCLUSION: Partial bladder outlet obstruction successfully created a hyperactive (unstable) bladder, typified by increased BC, RV, frequency of SA and a marked decrease in compliance. The greater BC, lower MP and frequency and amplitude of SA were prominent after the administration of BUP-4. Thus it is suggested that BUP-4 effectively inhibited bladder instability in rats induced by infravesical outlet obstruction and was more effective than oxybutynin in increasing BC.     

Biochemical evaluation of obstructive bladder dysfunction in men secondary to BPH: a preliminary report

OBJECTIVES: In the rabbit, two of the major cellular alterations that mediate bladder dysfunction secondary to partial outlet obstruction are a decreased ability of the sarcoplasmic reticulum (SR) to store and release Ca2+, and mitochondrial dysfunction. The objective of the current study was to determine whether SR and mitochondrial dysfunctions are associated with symptomatic benign prostatic hyperplasia (BPH) in men. METHODS: Bladder biopsies were obtained from men with symptomatic BPH and from age-matched men with no urologic dysfunction. Each biopsy was analyzed for the following enzyme activities: malate dehydrogenase and citrate synthase (mitochondrial markers) and the sarcoplasmic reticular enzyme Ca2+ -dependent adenosine triphosphatase (ATPase). These values were compared with the enzyme activities of control rabbit bladder smooth muscle and bladder smooth muscle obtained from rabbits subjected to 2 weeks of partial outlet obstruction. RESULTS: The enzymatic activities of all three enzymes are significantly lower in human bladder smooth muscle than in rabbit bladder smooth muscle. The maximal activities of all three enzymes are significantly lower in human bladder samples obtained from men with diagnosed obstructive uropathy than in men of equal age with no urologic dysfunction. CONCLUSIONS: These studies demonstrate that similar to the response of the rabbit to partial outlet obstruction, obstructive dysfunction secondary to BPH is characterized by mitochondrial and SR dysfunction.     

Hepatic energy charge and adenine nucleotide status in rats anesthetized with halothane, isoflurane or enflurane

BACKGROUND: Volatile anesthetics are known to have varying effects on hepatic oxygen supply in vivo and have been shown to depress hepatic mitochondrial respiration and so energy charge in vitro. However, the effect of halothane, isoflurane and enflurane on hepatic adenine nucleotide status in vivo has not been evaluated. METHODS: Ninety male rats were exposed to 40% oxygen (n = 22) or 40% oxygen in equipotent (1 MAC) concentrations of halothane (1%) (n = 23), isoflurane (1.4%) (n = 22) or enflurane (2%) (n = 23) for 2 hours. All animals were then administered intraperitoneal pentobarbital and anesthesia continued and laparotomy was performed. A liver biopsy was taken for determination of hepatocellular adenosine-5-triphosphate (ATP), adenosine-5-diphosphate (ADP) and adenosine-5-monophosphate (AMP) and computation of energy charge (EC) from ?(ATP + 1/2ADP)+(ATP + ADP + AMP)? and total adenine nucleotides (TAN) from (ATP + ADP + AMP). After the biopsy the aorta was cannulated for blood sampling. RESULTS: Rats in each group were similar in weight, as well as acid base and blood gas status just after liver biopsy. Hepatic energy charge, ATP, ADP, AMP, and TAN levels were not different in animals receiving either halothane, isoflurane or enflurane when compared with those receiving only oxygen. CONCLUSION: One MAC of anesthesia for a period of 2 hours with the described volatile anesthetic agents did not affect adenine nucleotide status in vivo in rats.     

The effect of Helicobacter pylori infection on NSAID-related gastroduodenal damage in the elderly

The literature was reviewed to quantify the risk of complications related to the relief of obstruction in urinary retention. We also sought to determine whether the risk of complications is higher with rapid or gradual decompression (or "clamping") of the obstructed urinary bladder. The medical literature was identified by a search of the MEDLINE database and a manual review of the bibliographies of the identified articles. Studies show that, after quick, complete relief of obstruction, hematuria occurs in 2 to 16% of patients; however, clinically significant hematuria is rare. After relief of obstruction, blood pressure often decreases, but it usually normalizes and does not progress to clinically significant hypotension. Postobstructive diuresis occurs after relief of obstruction in 0.5 to 52% of patients; however, it is easily managed and rarely of clinical significance. We were unable to identify any randomized controlled studies that directly compared quick, complete emptying with gradual emptying of the obstructed bladder. Moreover, we identified no studies supporting the practice of gradual emptying of the obstructed bladder. The available published studies support quick, complete emptying for relief of the obstructed urinary bladder. We conclude that hematuria, hypotension, and postobstructive diuresis may occur after decompression of the obstructed urinary bladder, but these complications are rarely clinically significant. Quick, complete emptying of the obstructed bladder is safe, simple, and effective and is recommended as the optimal method for decompressing the obstructed urinary bladder. Prudent, supportive care is needed for all patients, with special attention to elderly patients and those with hypovolemia.     

Perspective: human immunodeficiency virus type 1 (HIV-1) RNA end points in HIV clinical trials: issues in interim monitoring and early stopping

PURPOSE: The objective of the study was to investigate specificity and sensitivity of bladder wall thickness in the diagnosis of bladder outlet obstruction. MATERIALS AND METHODS: The study included 174 patients referred to our prostate centers for lower urinary tract symptoms. Free uroflowmetry and pressure-flow studies were performed in duplicate as part of the diagnostic evaluation. After the 2 voiding studies were done the bladder was filled to 150 ml. and wall thickness was measured via suprapubic ultrasound. Bladder outlet obstruction was diagnosed and graded according to the Abrams-Griffiths and Sch?fer nomogram as well as to the group specific urethral resistance algorithm. RESULTS: A significant correlation (r > 0.6, p < or = 0.007) was found between bladder wall thickness and all parameters of the pressure-flow study. A bladder wall thickness of 5 mm. appeared to be the best cutoff point to diagnose bladder outlet obstruction, since 63.3% of patients with bladder wall thickness less than 5 mm. were unobstructed while 87.5% of those with a bladder wall thickness 5 mm. or greater were obstructed. Bladder wall thickness out performed uroflowmetry in terms of specificity and sensitivity in the diagnosis of outlet obstruction as demonstrated by an area under curve value of 0.860 versus 0.688 in the receiver operator characteristics analysis. CONCLUSIONS: Measurement of bladder wall thickness appears to be a useful predictor of outlet obstruction with a diagnostic value exceeding free uroflowmetry although it does not represent a substitution to invasive urodynamics. These data support the hypothesis that the relationships between morphology and function are of clinical importance.     

Changes in adenine nucleotide and mitochondrial metabolism of the kidney of burned rats and their relation to insulin

In rats with third-degree burns, the blood glucose level increased remarkably, with a concomitant suppression of insulin secretion from the pancreas after an oral glucose load. The energy charge (ATP + 1/2 ADP/ATP + ADP + AMP) levels of the kidney decreased to 0.659 as compared with 0.858 of controls at 8 hr after the burn (p less than 0.001). The phosphorylative activity of the kidney mitochondria fell to one third of controls at 8 hr after the burn (p less than 0.001), and that of heart mitochondria decreased to approximately 70% (p less than 0.005); the fall in liver and brain was less remarkable. The decrease in mitochondrial phosphorylative activity was accompanied by a reduction in the respiratory control ratio, P/O ratio, and state 3 respiration. The concentrations of cytochrome a(+a3) in the kidney mitochondria decreased to 69.9% of controls at 8 hr after the burn (p less than 0.001), those of cytochrome b to 82.6%, and those of cytochrome c + c1 to 75.3% (p less than 0.001). The decreased energy charge and oxidative phosphorylation of the kidney in burned rats were remarkably restored by subcutaneous administration of insulin. It is suggested that a reduction in insulin secretion from the pancreas may play an important role in initiating an impairment of adenine nucleotide and mitochondrial metabolism of the kidney.     

Cytoskeletal and cytocontractile protein composition of smooth muscle cells in developing and obstructed rabbit bladder

The differentiation patterns of smooth muscle cells (SMC) in rabbit bladder during development and in the hypertrophic response to partial outflow obstruction induced in adult animals were evaluated by biochemical and immunochemical techniques and by using a panel of monoclonal antibodies specific for desmin, vimentin, alpha-actin of smooth muscle (SM) type, SM myosin, and nonmuscle (NM) myosin isoforms. Desmin and SM alpha-actin were homogeneously distributed in SMC of developing, adult, and obstructed bladders. Conversely, marked changes in the ratio and antigenicity of SM myosin isoforms were observed by SDS electrophoresis and Western blotting, respectively. In particular, the 205 K (SM1) isoform was down-regulated with development whereas the 200 K (SM2) isoform was up-regulated around 7 days after birth and down-regulated in the obstructed bladder. Vimentin was expressed in SMC of the fetal bladder and declined markedly during postnatal, physiological hypertrophy of SMC, which occurs concomitantly with diminution of DNA synthesis. This polypeptide became detectable, however, in SMC of obstructed bladders. The 196 K (NM) myosin isoform recognized by NM-A9 antibody, present only in endothelium of blood vessels and in mucosa of normal fetal and adult bladders, became expressed in detrusor muscle, when SMC underwent a process of pathological hypertrophy. The reexpression of vimentin and the de novo appearance of NM myosin isoform in hypertrophic bladders can be reversed when the tissue mass is reduced, such as in bladders after 1-month recovery from partial obstruction. Thus, a specific NM myosin isoform can be used as a marker of SMC hypertrophy in obstructed bladder. In addition, the combined use of anti-vimentin and NM-A9 antibodies can distinguish between SMC which are in the physiological or in the pathological condition of adaptive bladder hypertrophy.     

Value of the shape of the flowmetry curve in the study of prostatism

OBJECTIVE: To determine the relation of the urinary flow curve morphology of free flowmetry with the status of lower urinary tract dynamics. METHODS: A mathematical model was designed to fit the urinary flow curves to two models: a symmetrical and an asymmetrical model. Based on these models we analyzed the relationship between the presence or absence of obstruction and the type of model which better adjusted the urinary flow curves in a series of 85 males. RESULTS: The urinary flow curves corresponding to absence of obstruction adjusted significantly better to a symmetrical model than those corresponding to bladder outlet obstruction. No correlation was observed between the type of curve and bladder contractibility or type of urinary obstruction. CONCLUSIONS: There is a relationship between the form of the urinary flow curve and bladder obstruction. In the absence of obstruction, the urinary flow curves are more symmetrical.     

Expression of neurotrophin-3 in the growing velvet antler of the red deer Cervus elaphus

Adenine phosphoribosyltransferase (APRT) from Saccharomyces cerevisiae was purified approximately 1500-fold. The enzyme catalyzes the Mg-dependent condensation of adenine and 5-phosphoribosylpyrophosphate (PRPP) to yield AMP. The purification procedure included anion exchange chromatography, chromatofocusing and gel filtration. Elution of the enzyme from the chromatofocusing column indicated a pI value of 4.7. The molecular mass for the native enzyme was 50 kDa; however, upon electrophoresis under denaturing conditions two bands of apparent molecular mass of 29 and 20 kDa were observed. We have previously reported the presence of two separate coding sequences for APRT, APT1 and APT2 in S. cerevisiae. The appearance of two bands under denaturing conditions suggests that, unlike other APRTs, this enzyme could form heterodimers. This may be the basis for substrate specificity differences between this enzyme and other APRTs. Substrate kinetics and product inhibition patterns are consistent with a ping-pong mechanism. The Km for adenine and PRPP were 6 microM and 15 microM, respectively and the Vmax was 15 micromol/min. These kinetic constants are comparable to the constants of APRT from other organisms.     

Cryotherapy of the resection edge after liver resection for colorectal cancer metastases

A 35-year-old female was referred to our clinic with a complaint of left flank pain in 1993. Drip infusion pyelography showed a filling defect of 25 x 24 mm in size in the left ureteropelvic junction. Computed tomography and ultrasonography revealed it as the renal stone. Percutaneous nephroureterolithotomy and extracorporeal shock-were lithotomy were performed. The stone was composed of 2,8-dihydroxyadenine (DHA). The patient was diagnosed as having a partial deficiency of adenine phosphoribosyltransferase (APRT) from the low APRT activity and a genotype of a compound heterozygote APRT*J/APRT*Q0 by T-cell analysis. The urinary excretion of 2,8-DHA crystals disappeared by the postoperative treatment with allopurinol. Cases of 2,8-DHA urolithiasis reported in the Japanese literature are discussed.     

Correlated effluxes of adenine nucleotides, Mg2+ and Ca2+ induced in rat-liver mitochondria by external Ca2+ and phosphate

The presence of inorganic phosphate and Ca2+ in the external medium induces a closely parallel efflux of both endogenous adenine nucleotides and Mg2+ from rat liver mitochondria. These effluxes are (a) pH-dependent and inhibited by uncouplers, respiration inhibitors and external Mg2+; (b) completely prevented by bongkrekate, but stimulated by atractylate. ATP, ADP or AMP each inhibit the release of Mg2+ promoted by Ca2+ and phosphate; however, in the presence of oligomycin and P1,P5-di(adenosine-5')-pentaphosphate (an inhibitor of adenylate kinase) only ADP is effective. Also the release of accumulated Ca2+ observed when approximately 50% Mg2+ is discharged is retarded by bongkrekate and added Mg2+ whereas it is accelerated by atractylate. All adenine nucleotides have a significant effect in retarding the efflux of accumulated Ca2+ but, in the presence of oligomycin and P1,P5-di(adenosine-5')-pentaphosphate, only ADP is active. From these results we conclude that effluxes of Mg2+, Ca2+ and adenine nucleotide from rat liver mitochondria induced by external phosphate are interconnected and regulated by external ADP and Mg2+ levels.     

Variability of clinical and pressure-flow study variables after 6 months of watchful waiting in patients with lower urinary tract symptoms and benign prostatic enlargement

PURPOSE: We quantified the physiological variability of clinical and pressure-flow study variables in patients with symptomatic benign prostatic enlargement. MATERIALS AND METHODS: Symptom scores were measured, and advanced urodynamic studies with pressure-flow analysis were performed in 178 patients before and 6 months after a period a watchful waiting. RESULTS: Patients without bladder outlet obstruction experienced significant symptomatic improvement. Symptoms in patients with obvious bladder outlet obstruction did not improve significantly. The reproducibility of mean pressure-flow variables was evident. However, there was an important intra-individual variability. Patients with obvious bladder outlet obstruction showed a significant decreases in detrusor pressure at maximal flow of 14cm. water, a significant decrease in the urethral resistance factor of 7 cm. water and a significant decrease of 1 obstruction class on the linear passive urethral resistance relation nomogram, indicating less severe bladder outlet obstruction. CONCLUSIONS: Mean differences among therapy groups must be regarded critically, especially when the difference are slight and possibly within physiological variability.     

Enhanced recovery from acute renal failure by the postischemic infusin of adenine nucleotides and magnesium chloride in rats

Although a number of manipulations prior to or during the initiation phase of an acute renal injury will modify the degree of functional impairment, agents administered after the acute insult usually have been ineffective. In the present study, adenine nucleotides (AMP, ADP, or ATP) combined with magnesium chloride were infused after an ischemic renal injury. Twenty-four hours later: (1) rats that received no infusion or one of the components of the mixture alone had reduced CIn (355 +/- 40 microliter/min/100 g of body wt vs. 977 +/- 40 control value), decreased RBF (3550 +/- 205 microliter/min/100 g of body wt vs. 5095 +/- 171 control value), elevated FENa (0.65 +/- 0.10% vs. 0.17 +/- 0.04 control value), and diminished UOsm (862 +/- 110 mOsm/kg vs. 1425 +/- 132 control value); (2) rats given dopamine or phenoxybenzamine maintained low CIn (365 +/- 50) despite improved RBF (4678 +/- 222); (3) rats infused with either AMP, ADP, or ATP combined with magnesium chloride had markedly improved CIn (594 +/- 44, P < 0.01), increased RBF (4269 +/- 223, P < 0.01); normalized FENa (0.18 +/- 0.07%, P < 0.01), and improved UOsm (1201 +/- 106 mOsm/kg, P < 0.05). In animals given no infusion or only magnesium chloride, ultrastructural studies demonstrated focal cellular necrosis and marked generalized tubular cell and mitochondrial swelling, whereas rats infused with ATP and magnesium chloride had fewer ultrastructural changes with better preservation of cellular morphology. Rats treated with ATP and magnesium chloride had improved CIn despite ischemic periods of 30, 45, and 60- min; and the degree of improvement was directly related to the quantity of ATP and magnesium chloride administered. The cellular content of exogenously administered ATP was 2.5 times greater in previously ischemic kidneys than in nonischemic kidneys. The data indicate that adenine nucleotides combined with magnesium chloride when infused after the initiation of acute renal failure significantly improve both CIn and tubular function and suggest that these agents effectively enhance recovery following an ischemc renal insult.     

Changes in overbite and face height from 5 to 45 years of age in normal subjects

Periodate-oxidized ADP (oADP)2 and periodate-oxidized ATP (oATP) stimulate the permeability transition in energized rat liver mitochondria measured as the Ca2+-efflux induced by Ca2+ and Pi. In the presence of Mg2+ and Pi, mitochondria lose intramitochondrial adenine nucleotides at a slow rate. oATP induces a strong decrease of the matrix adenine nucleotides which is inhibited by carboxyatractyloside. Under these conditions, Mg2+ prevents the opening of the permeability transition pore. EGTA prevents the Pi-induced slow efflux of adenine nucleotides, but is without effect on the oATP-induced strong decrease of adenine nucleotides. This oATP-induced strong adenine nucleotide efflux is inhibited by ADP. oATP reduces the increase of matrix adenine nucleotides occurring when the mitochondria are incubated with Mg2+ and ATP. This effect of oATP is also prevented by carboxyatractyloside. oATP is not taken up by the mitochondria. It is suggested that oATP induces a strong efflux of matrix adenine nucleotides by the interaction with the ADP/ATP carrier from the cytosolic side. The induction of the mitochondrial permeability transition by oADP and oATP is attributed to two mechanisms-a strong decrease in the intramitochondrial adenine nucleotide content, especially that of ADP, and a stabilization of the c-conformation of the ADP/ATP carrier.     

APT1, but not APT2, codes for a functional adenine phosphoribosyltransferase in Saccharomyces cerevisiae

The yeast Saccharomyces cerevisiae has two separate genes (APT1 and APT2) that encode two potentially different forms of adenine phosphoribosyltransferase (APRT). However, genetic analysis indicated that only APT1 could code for a complementing activity. Cloning and expression of both the APT1 and APT2 genes in Escherichia coli showed that although discrete proteins (APRT1 and APRT2) were made by these genes, only APRT1 had detectable APRT activity. Northern and Western blot analyses demonstrated that only APT1 was transcribed and translated under normal physiological conditions in yeast. Phylogenetic analysis revealed that APRT1 and APRT2 are evolutionary closely related and that they arise from a gene duplication event. We conclude that APT1 is the functional gene in S. cerevisiae and that APT2 is a pseudogene.     

Effects of liposteroid on skin lesions in autoimmune MRLlpr/lpr mice

Urine leakage from the umbilicus was observed while expressing urine by the Crede manoeuvre in a three-year-old tetraplegic girl with a chronically distended urinary bladder. Intravenous urography (IVU) revealed bilateral hydroureteronephrosis with markedly distended urinary bladder. Regular three hourly intermittent catheterization was advised, and the parents and carers of this child agreed to perform catheterization. There was cessation of urine leak within 48 hours of urethral drainage. Cystography performed two weeks later showed no vesicoureteric reflux; vesicoumbilical fistula was no longer demonstrable. Follow-up IVU, performed after eight and half months of regular intermittent catheterization, showed regression of hydroureteronephrosis. We believe that urine leakage from the umbilicus served two important protective functions in this child, viz. (1) it prevented possible vesical or renal rupture; (2) the striking clinical symptom of urine leak from the umbilicus focussed the attention of the carers to the underlying serious condition of the urinary tract. Further, this case demonstrates that regression of marked hydroureteronephrosis can be achieved by intermittent catheterization performed at regular intervals by devoted parents/carers, in selected cases of spinal cord injury with neuropathic bladder, and vesical outlet obstruction, thus obviating the need for any form of temporary or permanent urinary diversion.