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Biomedical subjects

K Persson

Publications and source records attributed to K Persson.

At least 145 records · Page 8Linked to original sources

Nitric oxide synthase and the lower urinary tract: possible implications for physiology and pathophysiology.

Inhibitory, relaxation-mediating, non-adrenergic, non-cholinergic (NANC) nerves and neurotransmission have been demonstrated in lower urinary tract smooth muscles, and evidence has accumulated that L-arginine-derived nitric oxide (NO) is responsible for the main part of this response. The NO-synthetizing enzyme, nitric oxide synthase (NOS), has been shown to be localized in nerve fibres of the detrusor, trigone, and urethra, but preferably in the outflow region. NOS seems to be colocalized with acetylcholine esterase, vasoactive intestinal peptide, and neuropeptide Y, which suggests that NO may have a role both as a directly acting transmitter and as a modulator of efferent neurotransmission. In addition, NO may be involved in afferent neurotransmission. It has been speculated that NO, released from nerves in the detrusor, could be one factor keeping the bladder relaxed during filling; however, the detrusor has a low sensitivity to NO and agents acting via the cyclic GMP system, which makes it less likely that NO has a role as a relaxant neurotransmitter in this tissue. This does not exclude that NO may modulate the effects on the detrusor of other transmitters, or that it has an afferent function. In contrast, NO effectively relaxes isolated smooth muscle preparations from the outflow region, suggesting that it may be involved in the decrease in intraurethral pressure observed at the start of normal micturition, and with the excessive urethral pressure variations ("unstable urethra"), which may be associated with certain voiding disturbances in women. The L-arginine/NO system may also control afferent activity in the outlet region, where lack of NO may lower the threshold for afferent firing leading to bladder instability. However, the functional importance of the L-arginine/NO system in the central and peripheral pathways controlling micturition remains to be established.

Animals↗

Non-adrenergic, non-cholinergic relaxation and levels of cyclic nucleotides in rabbit lower urinary tract.

Electrical field stimulation at 12 Hz produced urethral relaxation and increased the tissue cyclic GMP content by 111 +/- 36% (n = 6, P < 0.05). Pretreatment with zaprinast (10 microM) increased the tissue cyclic GMP content in response to electrical stimulation by 160 +/- 56% (n = 7, P < 0.05). The nitric oxide synthase inhibitor NG-nitro-L-arginine (0.1 mM) and methylene blue (50 microM) inhibited electrically-induced cyclic GMP accumulation. Methylene blue only partially inhibited urethral relaxation, whereas NG-nitro-L-arginine caused complete inhibition. Electrical stimulation of urethral preparations did not affect the tissue levels of cyclic AMP. Administration of sodium nitroprusside increased the cyclic GMP content in the urethra and detrusor. Administration of isoprenaline increased the detrusor cyclic AMP content, but no change in urethral cyclic AMP levels could be detected. Cyclic GMP related drugs (sodium nitroprusside, 8-bromo-cyclic GMP) reduced urethral tone by 67-75% and detrusor tone by 13-39%. These results suggest that nerve-induced relaxation of the rabbit urethra is associated with an increase in cyclic GMP, but not cyclic AMP content. Synthesis of NO is essential for both nerve-mediated relaxation and cyclic GMP accumulation. The urethral smooth muscle tissue is more sensitive to cyclic GMP-activating drugs than the detrusor smooth muscle.

Animals↗

Nucleotide sequence variations within the lipopolysaccharide biosynthesis gene gseA (Kdo transferase) among the Chlamydia trachomatis serovars.

The gene gseA, involved in the expression of the genus-specific epitope of chlamydial lipopolysaccharide (LPS), was analyzed by temperature gradient gel electrophoresis (TGGE) to visualize nucleotide sequence variations among the 15 serovars of Chlamydia trachomatis. Sequence analysis showed that the TGGE melting-profile patterns were able to detect single nucleotide variations within gseA and allowed the arrangement of the serovars in groups of both identical nucleotide sequences and sequences containing identical sites of nucleotide substitutions. Compared to serovar L2, four types of patterns were obtained: (i) serotypes A and Ba; (ii) B and C (causing endemic trachoma); (iii) D through K (causing sexually transmitted oculo-genital infections); (iv) L1 through L3 (the causative agents of lymphogranuloma venereum). A total of 58 isolated of C. trachomatis of genital or conjunctival origin were tested by this method in comparison to reference strains. Forty-eight isolates (13 of type E, 16 of type F, nine of type G, and ten of type K) yielded the same melting profile as the corresponding type strain, independent of whether they were isolated from genital or ocular infections. However, ten B serotype strains of genital origin behaved in TGGE like a typical genital strain and not a trachoma strain. Thus, although gseA was found to be highly conserved among C. trachomatis, the obtained TGGE profiles of the tested strains tended to correlate with their specific site of infection.

Amino Acid Sequence↗

Nitric oxide synthase and nitric oxide-mediated effects in lower urinary tract smooth muscles.

In the lower urinary tract smooth muscles, both excitatory and inhibitory non-adrenergic, non-cholinergic (NANC) nerves and neurotransmission can be demonstrated. An inhibitory, relaxation-mediating system may serve not only the detrusor, the trigone, and the bladder neck/urethra, but may also be of importance for their integrated function. Available data suggest that nitric oxide synthase (NOS) is localized in nerve fibres of the lower urinary tract, preferably in the outflow region, and evidence has accumulated that L-arginine-derived nitric oxide (NO) is responsible for the main part of the inhibitory NANC response. Coinciding localization of NOS positive nerves with nerves expressing acetylcholine esterase, vasoactive intestinal peptide, and neuropeptide Y, suggests that NO may have a role both as a directly acting transmitter and as a modulator of efferent neurotransmission. In addition, NO may be involved in afferent neurotransmission. Theoretically, NO released from nerves in the detrusor, could be one factor keeping the bladder relaxed during filling. However, the detrusor has a low sensitivity to NO and agents acting via cyclic GMP, which makes it less likely that NO has a role as a relaxant neurotransmitter. This does not exclude that NO may modulate the effects of other transmitters, or that it has an afferent function. NO effectively relaxes isolated smooth muscle preparations from the outflow region, suggesting that it may be involved in the decrease in intraurethral pressure associated with normal micturition, and with the excessive urethral pressure variations ("unstable urethra"), which may be associated with certain voiding disturbances in women.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Oxidoreductases↗

Some pre- and postjunctional effects of castration in rabbit isolated corpus cavernosum and urethra.

Pre- and postjunctional effects of castration were investigated in isolated corpus cavernosum (CC) and prostatic and preprostatic urethral preparations obtained from rabbits that had been castrated surgically 14 days before investigation. Preparations obtained from untreated animals were used as controls. Castration did not change the relaxing effects of SIN-1 (NO donor) or papaverine in CC preparations contracted by noradrenaline (NA). Electrical field stimulation of CC preparations contracted by NA or endothelin-1 produced frequency-dependent and tetrodotoxin-sensitive relaxations. As compared with controls, the electrically induced relaxations were increased in preparations from castrated animals. Pretreatment with prazosin increased the electrically induced relaxations in CC from untreated rabbits, but had no effect on preparations from castrated animals. In CC preparations incubated with 3H-NA, castration significantly reduced the electrically evoked release of 3H. L-NOARG, an inhibitor of NO synthase, had no effect on 3H-efflux. In prostatic, but not preprostatic, urethral preparations contracted by NA, the relaxant effects of SIN-1 and vasoactive intestinal polypeptide were significantly smaller following castration. Furthermore, castration significantly reduced electrically evoked relaxations in prostatic urethral preparations contracted by NA, while in preprostatic urethra, no such effect was seen. Castration or L-NOARG had no effect on the electrically induced release of 3H-NA in either of the urethral tissues. The results suggest that the hormonal changes caused by castration may modulate the functional effects in vitro of some parts of the urogenital tract. In penile erectile tissue, the relaxations induced by electrical field stimulation are increased, probably for the most part through a decrease in the neuronal release of NA. In prostatic urethra, on the other hand, electrically evoked relaxations are decreased, possibly as a result of an impaired ability of the smooth muscle itself to respond to relaxant agents. In preprostatic urethra, castration has no obvious functional effects. The physiological consequences of these findings in the in vivo situation remain to be established.

Animals↗

ACE inhibitors and their influence on inflammation, bronchial reactivity and cough.

Orally active angiotensin converting enzyme (ACE) inhibitors have been successfully used in the treatment of congestive heart failure and hypertension. However, adverse skin reactions, such as angioneurotic oedema have been reported following such medication. Furthermore, these drugs have been associated with a persistent dry cough in subjects without previous known bronchial hyper-reactivity. There is reason to believe that an ACE inhibitor-induced cough is due to an irritant inflammatory state in the airways of susceptible individuals and that this might have pathophysiological features in common with the cough seen as an early symptom of asthma. All inflammatory responses--wheal and flare reactions, airway reactivity, and infiltration by neutrophils and eosinophils--were enhanced by ACE inhibitors in a dose-dependent manner. Other ACE inhibitors might have different proinflammatory profiles.

Adult↗

Antiatherosclerotic effects of the angiotensin-converting enzyme inhibitors captopril and fosinopril in hypercholesterolemic minipigs.

We evaluated the two angiotensin-converting enzyme (ACE) inhibitors captopril and fosinopril with regard to possible antiatherosclerotic effects in minipigs. Experimental hypercholesterolemia and atherosclerosis was produced in 33 minipigs of the Göttingen strain by an egg yolk/cholesterol-enriched diet for 1 year. One group (n = 11) was fed the atherogenic diet alone and served as a control. A second group (n = 11) received captopril (80 mg/kg/day) added to the atherogenic diet, and a third group (n = 11) was treated in the same manner but with fosinopril (8 mg/kg/day). The drug treatments produced significant reduction in serum ACE activity associated with a reactive increase in plasma renin activity (PRA), but had only minor effects on plasma lipids and lipoproteins. At the end of the treatment period, all animals were killed and examined for degree of atherosclerosis. The percentage of atherosclerotic area in the abdominal aorta was significantly lower in both drug-treated groups as compared with controls. Furthermore, accumulation of cholesterol in the thoracic and abdominal aorta was inhibited by drug treatment. Finally, the percentage of intimal thickening in abdominal aorta was significantly reduced in the drug-treated groups. In conclusion, the ACE inhibitors captopril and fosinopril inhibited development of atherosclerosis in hypercholesterolemic minipigs.

Aldosterone↗

Occurrence of antibodies against chlamydial lipopolysaccharide in human sera as measured by ELISA using an artificial glycoconjugate antigen.

An artificial glycoconjugate containing, as a ligand, the deacylated carbohydrate backbone of a recombinant Chlamydia-specific lipopolysaccharide was used as a solid-phase antigen in ELISA to measure antibodies against chlamydial LPS. The specificity and reproducibility of the assay was shown by using a panel of prototype monoclonal antibodies representing the spectrum of antibodies also occurring in patient sera. These mAbs recognized Chlamydia-specific epitopes [alpha 2-->8-linked disaccharide of 3-deoxy-D-manno-octulosonic acid (Kdo) or the trisaccharide alpha Kdo-(2-->8)-alpha Kdo-(2-->4)-alpha Kdo] or those shared between chlamydial and Re-type LPS (alpha Kdo, alpha 2-->4-linked Kdo disaccharide). The assay was used to measure IgG, IgA and IgM antibodies against chlamydial LPS in patients with genital or respiratory tract infections. In comparison to the results obtained with sera from blood donors, it became evident that both types of infection result in significant changes in the profile of LPS antibodies.

Antibodies, Bacterial↗

Angiotensin converting enzyme inhibitors and atherosclerosis.

This study was designed to evaluate possible antiatherosclerotic effects of angiotensin converting enzyme inhibitors in mini-pigs. Experimental hypercholesterolemia and atherosclerosis were produced in mini-pigs of the Göttingen strain by adding 11% egg yolk and 1% cholesterol to the diet for 52 weeks. The animals were divided into three groups. One group was fed the atherogenic diet alone and served as control. The second group was treated with captopril in a dose of 80 mg/kg/day added to the atherogenic diet on an individual basis. The third group was treated with fosinopril in a dose of 8 mg/kg/day. Both drugs produced a significant reduction in serum ACE activity associated with a reactive rise in plasma renin activity and a slight fall in serum aldosterone concentration. The drug treatment had only minor effects on plasma lipids. The aorta and the carotid and coronary arteries were examined for atherosclerotic lesions. Atherosclerotic plaques developed in the abdominal aorta whereas fatty streaks were present in the thoracic aorta and the coronary arteries. Both drugs significantly reduced the percent visible atherosclerosis in the abdominal aorta. Furthermore, the accumulation of cholesterol in the thoracic and abdominal aorta was significantly reduced. The effect of captopril and fosinopril on endothelium-dependent relaxation of iliac arteries was examined. After addition of 3 x 10(-7) M acetylcholine strips from basal diet fed mini pigs showed a remaining tension of 7.0% +/- 7.1 (p < 0.05 compared to cholesterol-high diet), cholesterol-high diet 36.4% +/- 10.2, captopril 16.9% +/- 4.9 (p < 0.01) and fosinopril 31.7% +/- 4.6 (n.s.). It is concluded that the ACE inhibitors captopril and fosinopril inhibited the development of atherosclerosis in hypercholesterolemic mini-pigs.

Acetylcholine↗

Lack of evidence of a relationship between genital symptoms, cervicitis and salpingitis and different serovars of Chlamydia trachomatis.

Isolates of Chlamydia trachomatis from 424 women were serotyped, and signs and symptoms related to the infecting serovar. Symptoms suggesting genital chlamydial infection were present in 37% of the women, while 15% had clinical findings consistent with lower genital tract infection or ascending infection. Cervicitis, adnexal tenderness and salpingitis were not associated with any specific serovar. On the contrary, the various clinical manifestations tended to occur at similar rates with the different serovars, suggesting a similar pathogenic potential of the serovars detected.

Adult↗

Effects of certain inflammatory mediators on bovine neutrophil migration in vivo and in vitro.

Migration of bovine neutrophils towards endotoxin, recombinant bovine interleukin-1 beta (rBoIL-1 beta), recombinant human tumor necrosis factor-alpha (rhTNF-alpha), platelet-activating factor (PAF), complement factor C5a, leukotriene B4 (LTB4), and recombinant human interleukin-8 (rhIL-8) was studied in vivo, using the teat cistern model, and in vitro using the modified Boyden chamber method. Infusion of endotoxin, rBoIL-1 beta, rhTNF-alpha, PAF, or C5a into the teat cistern induced significant accumulation of leukocytes, mainly neutrophils, during the sampling period. Endotoxin was, on a molar basis, the most potent inducer of cell accumulation in vivo, followed by rBoIL-1 beta, while C5a, PAF and rhTNF-alpha were less potent. No significant cell accumulation was observed after infusion of LTB4 or rhIL-8. A significant migration of cells into the teat cistern was first observed 2 h after the infusion of endotoxin or rBoIL-1 beta, the rBoIL-1 beta-induced response started somewhat earlier. The first significant cell accumulation after infusion of PAF or C5a was observed already 1.5 h post infusion. The largest numbers of cells were reached 2.5-4.5 h after the infusion of endotoxin, rBoIL-1 beta, rhTNF-alpha, PAF or C5a. In vitro, significant migration of bovine blood neutrophils was observed towards C5a or rhIL-8, and to a lower extent towards LTB4, while no chemotactic response to endotoxin, rBoIL-1 beta, rhTNF-alpha, and PAF was observed. Possible roles of the different substances as inducers of neutrophil migration into the bovine teat are discussed.

Animals↗

Characterization of Listeria strains isolated from soft cheese.

Three soft cheeses were exposed to quantitative analysis for listeria and found to contain a large number of listeria. Thirty-five of the listeria strains isolated from the three cheeses were characterized by use of biochemical tests, serotyping, phagetyping and DNA restriction enzyme analysis. Seven isolates were identified as Listeria innocua and 28 as Listeria monocytogenes. Two to four different clones of L. monocytogenes could be identified from each cheese. In contrast, only one clone could be detected among the L. innocua isolates. From an epidemiological point of view the findings of different clones of L. monocytogenes in the same cheese emphasize the need for typing several listeria isolates from one and the same food sample. It is concluded that the best overview of the population of the listeria strains is obtained after direct plating of the sample followed by enumeration, isolation and extensive typing.

Bacteriophage Typing↗

Endothelin-1-induced phosphoinositide hydrolysis and contraction in isolated rabbit detrusor and urethral smooth muscle.

1. Endothelin-1 (ET-1) caused a concentration-dependent increase in the formation of inositol phosphates (IPs) in isolated rabbit detrusor and urethral smooth muscle preparations prelabelled with myo-[3H]inositol. 2. The increase in accumulation of IPs was slow in onset in both detrusor and urethra, with no significant accumulation demonstrable during the first 30 min. The increase in IPs accumulation found after exposure of detrusor tissue to ET-1 (10(-7) M) for 2 hr (250 +/- 38%, n = 7) was not significantly different from that found in the urethra (279 +/- 40%, n = 6), when expressed as per cent of corresponding control values. 3. Pretreatment with nifedipine (10(-6) M) did not reduce IPs formation. In contrast, no increase in IPs formation was demonstrated in Ca(2+)-free medium. 4. ET-1 (10(-11)-10(-7) M) produced concentration-dependent, slowly developing contractions in both detrusor and urethral preparations. Pretreatment with H-7 (3 x 10(-5) M) for 30 min before ET-1 application resulted in a non-parallel shift of the ET-1 concentration-response curve with significant reductions in maximal responses in both tissues. 5. ET-1-induced contractions in urethral preparations were markedly inhibited by Ni2+ (3 x 10(-4) M), whereas the effect of Ni2+ in the detrusor was less pronounced. 6. The results suggest that ET-1 stimulates phosphoinositide hydrolysis in the rabbit detrusor and urethra. Both IPs formation and contractile activation evoked by ET-1 are dependent on extracellular Ca2+.(ABSTRACT TRUNCATED AT 250 WORDS)

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Facilitatory effect of vasoactive intestinal polypeptide on spinal and peripheral micturition reflex pathways in conscious rats with and without detrusor instability.

In unanesthetized, normal rats, and rats with bladder hypertrophy following infravesical outflow obstruction, cystometry was performed to investigate the effects of spinal and peripheral administration of vasoactive intestinal polypeptide (VIP) on micturition. In addition, the direct effects of the peptide on isolated smooth muscle preparations of detrusor and urethra were studied. In normal animals, 10 micrograms. of VIP administered intrathecally as well as intra-arterially close to the bladder, but not intravenously, decreased micturition volume and bladder capacity, and facilitated spontaneous bladder contractions. In animals with bladder hypertrophy, the same dose of VIP intrathecally had similar effects on these three parameters, but the effects of VIP given intra-arterially were less pronounced. VIP given intravenously was ineffective. Hexamethonium 5 mg. x kg.-1 given intraarterially did not block the stimulatory effect of VIP 10 micrograms. given intra-arterially to normal animals. VIP had negligible effects on isolated detrusor muscle contracted by carbachol or electrical stimulation, or on urethral preparations contracted by noradrenaline. These results suggest that VIP has a facilitatory action on the micturition reflex at the spinal cord and ganglionic levels.

Animals↗