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PubMedDate not supplied

[Polarization state of the light source and determination of attenuated total internal reflection spectra in intact microorganisms].

The problems are considered of the interaction of linear polarized light current with undestroyed microorganisms while recording the spectra of attenuated total refraction(ATR) and repeated ATR (RATR). It is shown that proper allowance should be made of dichrosim of absorption bands of microorganisms during quantitative studies. Peculiarities of obtaining RATR spectra of the linearly polarized light source with polarization azinut other than 0 and 90 degrees are considered.

Actinomyces↗
PubMed2001

Magnetic resonance imaging after operative repair of achilles tendon rupture.

We performed a magnetic resonance imaging (MRI) study in 16 consecutive patients who had undergone open repair of a unilateral Achilles tendon rupture (ATR) at an average of 32.5 (SD 3.2) (range 29-36) months from the operation. We measured the widest antero-posterior diameter of the tendon, the longest distance between the insertion of the Achilles tendon on the calcaneum and the musculo-tendinous junction of the soleus muscle on the Achilles tendon, the distance between the insertion of the Achilles tendon on the calcaneum and the point of maximal width of the tendon. We also ascertained whether areas of altered signal were present in and around the tendon. The operated tendons were always significantly thicker than the non-operated ones. There was a non-significant trend for the other measurements to be greater in the operated tendons. In five patients, areas of dishomogeneous signal were present in the operated tendon. These areas were less than 25% of the antero-posterior diameter of the tendon, and were clinically silent. These findings probably represent normal features of long-term tendon healing following open repair of an ATR.

Achilles Tendon↗
PubMed2001

Replication protein A2 phosphorylation after DNA damage by the coordinated action of ataxia telangiectasia-mutated and DNA-dependent protein kinase.

Replication protein A (RPA, also known as human single-stranded DNA-binding protein) is a trimeric, multifunctional protein complex involved in DNA replication, DNA repair, and recombination. Phosphorylation of the RPA2 subunit is observed after exposure of cells to ionizing radiation (IR) and other DNA-damaging agents, which implicates the modified protein in the regulation of DNA replication after DNA damage or in DNA repair. Although ataxia telangiectasia-mutated (ATM) and DNA-dependent protein kinase (DNA-PK) phosphorylate RPA2 in vitro, their role in vivo remains uncertain, and contradictory results have been reported. Here we show that RPA2 phosphorylation is delayed in cells deficient in one of these kinases and completely abolished in wild-type, ATM, or DNA-PK-deficient cells after treatment with wortmannin at a concentration-inhibiting ATM and DNA-PK. Caffeine, an inhibitor of ATM and ATM-Rad3 related (ATR) but not DNA-PK, generates an ataxia-telangiectasia-like response in wild-type cells, prevents completely RPA2 phosphorylation in DNA-PKcs deficient cells, but has no effect on ataxia-telangiectasia cells. These observations rule out ATR and implicate both ATM and DNA-PK in RPA2 phosphorylation after exposure to IR. UCN-01, an inhibitor of protein kinase C, Chk1, and cyclin-dependent kinases, has no effect on IR-induced RPA2 phosphorylation. Because UCN-01 abrogates checkpoint responses, this observation dissociates RPA2 phosphorylation from checkpoint activation. Phosphorylated RPA has a higher affinity for nuclear structures than unphosphorylated RPA suggesting functional alterations in the protein. In an in vitro assay for DNA replication, DNA-PK is the sole kinase phosphorylating RPA2, indicating that processes not reproduced in the in vitro assay are required for RPA2 phosphorylation by ATM. Because RPA2 phosphorylation kinetics are distinct from those of the S phase checkpoint, we propose that DNA-PK and ATM cooperate to phosphorylate RPA after DNA damage to redirect the functions of the protein from DNA replication to DNA repair.

Androstadienes↗
PubMed2002

Genes involved in DNA repair are mutational targets in endometrial cancers with microsatellite instability.

Microsatellite instability (MSI) is observed in a subset of endometrial cancers (ECs) and is attributed to defects in mismatch repair. Mismatch repair deficiency allows for accumulation of mutations in the coding repeats of key target genes, which may be involved in the initiation and progression of MSI+ EC. We examined genes implicated in DNA repair pathways in 38 MSI-high (MSI-H), 10 MSI-low, 25 microsatellite stable ECs, and a selected panel of associated premalignant hyperplasias. Genetic alterations were correlated to histopathological data, including tumor grade and stage. Somatic frameshift mutations were observed in hMLH3, hMSH3, hMSH6, CHK1, and BAX genes in MSI-H endometrial hyperplasias and cancers, whereas mutations in ATR and CDC25C were observed only in MSI-H ECs. Increased mutation frequency in DNA damage response pathway genes including ATR, CHK1, and BAX demonstrated a significant trend with advancing tumor grade (P < 0.05). Our observations of the same mutations at short coding mononucleotide repeats in both premalignant lesions and tumors and association of increased frequency of mutation accumulation with advancing tumor grade suggest that these alterations may play a role in the development and progression of MSI+ EC.

Adenocarcinoma↗
PubMed2002

Determinants of afterload-induced diastolic dysfunction.

Severe left ventricular (LV) afterload elevations induce diastolic dysfunction (DD). This decompensatory response, observed in both dogs and rabbits, seems to be related to cytosolic calcium levels. As rats have different calcium kinetics, we investigated the effects of acute LV afterload elevation in rats. Anaesthetized Wistar rats (n = 10) were instrumented in order to record simultaneously LV pressure and septal-free wall dimensions. Afterload was elevated through partial or total occlusions of the ascending aorta. In afterloaded heartbeats, we measured the time constant tau, the necessary (NTR) and the available (ATR) time intervals to complete LV relaxation. DD was evaluated through analysis of the position of the end-diastolic pressure-volume relation. Afterload elevations elicited acceleration of relaxation and DD was observed only in isovolumetric heartbeats. This DD could be explained by the deficit in time to complete relaxation in isovolumetric heartbeats. We conclude, therefore, that the time constant tau and ATR are the major determinants of afterload-induced DD. The calcium kinetics of the rat provide a better adaptation to afterload elevations in this than in other species.

Animals↗
PubMed2002

[Functional analysis of yeast homologue gene associated with human DNA helicase causative syndromes].

Proteins having DNA helicase activity play very important roles in many processes involving DNA workings such as replication, repair, and recombination. In this decade, many DNA helicase genes have been cloned as the causative genes of human recessive heredity diseases. These are the causative genes for Xeroderma pigmentosum (XPB and XPD), Cockayne syndrome (CSB), diffuse collagen disease (Ku80), alpha-thalassmia (ATR-X), Bloom syndrome (BLM), Werner syndrome (WRN) and Rothmund-Thomson syndrome (RTS). The yeast homologue genes of these human DNA helicase genes exist. S. cerevisiae RAD25/SSL2, RAD3, RAD26, YKU80/HDF2 and RAD54 are the homologue for XPB/ERCC3, XPD/ERCC2, CSB/ERCC6, Ku80/XRCC5 and ATR-X/HX2, respectively. E coli. recQ gene and S. cerevisiae SGS1 are the homologue for all BLM, WRN and RTS. A search of whole genome of S. cerevisiae revealed that SGS1 is the sole homologue of recQ in S. cerevisiae. Thus it seems likely that SGS1 is a functional homologue of one or several human RecQ family genes. Many basic or essential functions are well conserved in the cells from lower eukaryotic to higher mammalian. The functional analysis in yeast could make an useful insight for the human homologue. To clarify the functions of S. cerevisiae Sgs1 and to get an insight into the functions of Blm, Wrn and Rts, in this study, we analyzed the phenotype of sgs1 disruptant and in detail the cause of the poor sporulation phenotype of sgs1 disruptants in relation to meiotic processes including meiotic recombination. The poor sporulation of sgs1 disruptants was complemented with a mutated SGS1 gene encoding a protein lacking DNA helicase activity; however, the mutated gene could suppress neither the sensitivity of sgs1 disruptants to methyl methanesulfonate (MMS) and hydroxyurea nor the mitotic hyperrecombination phenotype of sgs1 disruptants. The N-terminal 1-45 amino acid region and 698-1195 amino acid region of Sgs1, which including helicase domain and C-terminal RecQ conserved region with helicase activity, were required for complementation of MMS sensitivity and suppression of hyperrecombination of sgs1 disruptants in mitotic growth. The 126-400 and 596-1195 amino acid regions of Sgs1 were required for complementation of poor sporulation and of reduced meiotic functions. These regions required for the mitotic or meiotic functions of Sgs1 were well overlapped with the interaction regions of Top3 and Top2. Some of these results might explain the mechanism of the symptom of RecQ-related syndromes.

Adenosine Triphosphatases↗
PubMed2003

Enhanced radiation and chemotherapy-mediated cell killing of human cancer cells by small inhibitory RNA silencing of DNA repair factors.

Recent developments in the use of small inhibitory RNA molecules (siRNAs) to inhibit specific protein expression have highlighted the potential use of siRNA as a therapeutic agent. The double-strand break signaling/repair proteins ATM, ATR, and DNA-dependent protein kinase catalytic subunit (DNA-PK(cs)) are attractive targets to confer enhanced radio and chemosensitivity to tumor cells. We have designed and exogenously delivered plasmids encoding siRNAs targeting these critical kinases to human cancer cells to assess the feasibility of this concept as a clinically translatable experimental therapeutic. siRNA led to a approximately 90% reduction in target protein expression. siRNAs targeting ATM and DNA-PK(cs) gave rise to a dose-reduction factor of approximately 1.4 compared with untransfected and control vector-transfected cells at the clinically relevant radiation doses. This was greater than the radiosensitivity achieved using the phosphatidylinositol 3'-kinase inhibitor Wortmannin or DNA-PK(cs) competitive inhibitor LY294002. A similar increased sensitivity to the alkylating agent methyl methanesulfonate (MMS) was also observed for siRNA-mediated ATR silencing. Together, these data provide strong evidence for the potential use of siRNA as a novel radiation/chemotherapy-sensitizing agent.

Ataxia Telangiectasia Mutated Proteins↗
PubMed2003

[Oleyl pyroglutamate for use as transdermal enhancer and its enhancing mechanism].

AIM: To test the enhancing activity and the mechanism of oleyl pyroglutamate used as transdermal enhancer. METHODS: The penetration-enhancing effects of oleyl pyroglutamate, oleyl alcohol and oleic acid on the three drugs (caffeine, tinidazole and cortisone) were observed; the transdermal enhancing mechanism of oleyl pyroglutamate was studied with the attenuated total reflectance Fourier-transfer infrared spectroscopy(ATR-FTIR) of the human stratum corneum in vivo. RESULTS: The penetration-enhancing ratio of the three drugs was 7.9 fold, 41.8 fold and 2.8 fold, respectively. The absorptions at 2,800-2,950 cm-1 and 1,642-1,646 cm-1 (amide-I) in the ATR-FTIR spectrum of the stratum were found to be shifted differently following removal of the stratum corneum which was treated with oleyl pyroglutamate. CONCLUSION: Oleyl pyroglutamate showed better penetration-enhancing effect on the penetration of drugs. Its transdermal enhancing mechanism may be that oleyl pyroglutamate induced not only disordering of the stratum corneum lipid, but also change of the secondary structure of keratin.

Administration, Cutaneous↗
PubMed1992

[The role of muscarinic receptor subtypes in feline tracheal submucosal gland secretion].

To determine what muscarinic receptor subtype regulates the rise of intracellular calcium concentration ([Ca2+]i) and resultant airway submucosal gland secretion on muscarinic receptor stimulation, we examined the effects of atropine (ART), pirenzepine (PZ), 11([2-(diethylamino) methyl-1-piperidinyl] acetyl)-5,11-dihydro-6H-pirido (2,3-b)(1,4)-benzodiazepine-6-one (AF-DX116) and 4-diphenylacetoxy-N-methylpiperidine methiodode (4-DAMP) on methacholine (MCh)-evoked [Ca2+]i rise in acinar cells, mucus glycoprotein (MGP) secretion and electrolyte secretion from submucosal glands isolated from feline tracheae. [Ca2+]i was measured with the Ca(2+)-sensitive fluorescent dye, fura2. We determined MGP secretion by measuring trichloroacetic acid (TCA)-precipitable 3H-labeled glycoconjugates and electrolyte secretion by the change in the rate constant of 22Na-efflux from isolated glands. Half maximal inhibitory concentrations (IC50) of PZ, AF-DX116, 4-DAMP and ATR against MCh (10(-5) M)-evoked [Ca2+]i rise were 10(-7) M, 6 x 10(-6) M, 8 x 10(-9) M and 6 x 10(-9) M, respectively. IC50 values of these antagonists against MCh (10(-5) M)-evoked MGP secretion were 10(-6) M, 2 x 10(-5) M, 8 x 10(-9) M and 6 x 10(-9) M, respectively. MCh (10(-5) M)-evoked 22Na-efflux was significantly inhibited by 10(-7) M 4-DAMP and 10(-7) M ATR (p < 0.01, respectively), but the inhibitory effect of PZ (10(-7) M) was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2004

Atrial-selective antiarrhythmic actions of novel Ikur vs. Ikr, Iks, and IKAch class Ic drugs and beta blockers in pigs.

BACKGROUND: The Kv1.5 channel, underlying IKur, is supposed to be atrial selective in pigs and humans. We investigated the effects of different potassium channel blockers, i.e. the IKur blockers AVE 0118, S9947 and S20951, with amiodarone (AM), dofetilide (DO), azimilide (AZ), ibutilide (IB), the IKs blocker HMR 1556, atropine (ATR), flecainide (FL), propafenone (PR), d,l-sotalol (SO), atenolol (ATE), and esmolol (ES), on the left and right atrial and ventricular refractoriness and left atrial vulnerability (LAV) in vivo in pigs. MATERIAL/METHODS: In pentobarbital-anesthetized pigs (n=81), atrial and ventricular effective refractory periods (ERPs) were measured with the S1-S2-extrastimulus-method and QTc time from electrocardiograms. LAV was assessed after S2-extrastimulus to the left atrium. RESULTS: All IKur blockers prolonged left stronger than right atrial ERP and did not change QTc. All IKr blockers predominantly prolonged the right vs. left atria. AM prolonged both atria equally, and ATR the left only. Pure beta blockers acted predominantly on the left atrium, as did FL and PR, while d,l-sotalol acted predominantly on the right. AVE 0118, S9947, S20951, ibutilide, and d,l-sotalol significantly decreased LAV (-100%, -100%, -82%, -53%, -42%; p<0.05), in contrast to all other drugs. CONCLUSIONS: The IKur blockers exhibited stronger effects on the left atrium, which itself has shorter refractoriness, but strikingly with no effect on ventricular repolarization, while IKr blockers, IKs blockers, and d,l-sotalol exerted predominantly right atrial effects and known ventricular effects. IKur blockers inhibited atrial tachyarrhythmias stronger than all available drugs. Therefore, IKur blockers seem to be promising new atrial-selective antiarrhythmic drugs.

Adrenergic beta-Antagonists↗
PubMed2004

CHK1 and CHK2 are differentially involved in mismatch repair-mediated 6-thioguanine-induced cell cycle checkpoint responses.

The DNA mismatch repair (MMR) system plays an important role in mediating a G2-M checkpoint arrest and subsequent cell death following treatment with a variety of chemotherapeutic agents. In this study, using 6-thioguanine (6-TG) as a mismatch-inducing drug, we examine the role of ataxia telangiectasia mutated (ATM)/CHK2 and ATM and Rad-3 related (ATR)/CHK1 signaling pathways in MMR-mediated cell cycle responses in MMR-proficient human colorectal cancer RKO cells. We show that, in response to 6-TG (3 micromol/L x 24 hours), activating phosphorylation of CHK1 at Ser317 [CHK1(pS317)] and CHK2 at Thr68 [CHK2(pT68)] are induced differentially during a prolonged course (up to 6 days) of MMR-mediated cell cycle arrests following 6-TG treatment, with CHK1(pS317) being induced within 1 day and CHK2(pT68) being induced later. Using chemical inhibitors and small interfering RNA of the signaling kinases, we show that a MMR-mediated 6-TG-induced G2 arrest is ATR/CHK1 dependent but ATM/CHK2 independent and that ATR/CHK1 signaling is responsible for both initiation and maintenance of the G2 arrest. However, CHK2(pT68) seems to be involved in a subsequent tetraploid G1 arrest, which blocks cells that escape from the G2-M checkpoint following 6-TG treatment. Furthermore, we show that CHK2 is hyperphosphorylated at later times following 6-TG treatment and the phosphorylation of CHK2 seems to be ATM independent but up-regulated when ATR or CHK1 is reduced. Thus, our data suggest that CHK1(pS317) is involved in a MMR-mediated 6-TG-induced G2 arrest, whereas CHK2(pT68) seems to be involved in a subsequent tetraploid G1-S checkpoint. The two signaling kinases seem to work cooperatively to ensure that 6-TG damaged cells arrest at these cell cycle checkpoints.

Antimetabolites, Antineoplastic↗
PubMed2002

The validity of clinical examination in adolescent spinal deformities.

STUDY DESIGN: retrospective study on the accuracy and reliability of two clinical tests for scoliosis in young patients. AIM: to evaluate the inter-observer reliability of three non-invasive clinical measurements: hump height (HH), axial trunk rotation (ATR), and distance of the spinous process from the plumb line (DP) in standing; to compare these results with the corresponding radiographic measurements, the Cobb angles (CA). POPULATION: 116 patients, 78 females and 38 males; 410 examinations have been performed (144 patients with brace and 266 without). METHODS: a database was created using the measurements of different clinical parameters obtained from two examiners that measured them independently and in the same conditions. The Cobb method has been used as a gold standard. RESULTS: our results show a very high inter-rater reliability for HH and ATR measurements. The DP shows a different inter-rater reliability for the thoracic (C7) and lumbar (L3) spine, in both cases lower than that in the frontal plane; the ICC of the thoracolumbar DP (D12) was very low. The correlation with the radiographic value was weak.

Adolescent↗
PubMed2004

Resistant arterial hypertension and hyperlipidemia: atorvastatin, not vitamin C, for blood pressure control.

BACKGROUND: Hypertension is considered resistant if blood pressure cannot be reduced to <140/90 mmHg with an appropriate triple-drug regimen, including an oral diuretic, with all agents administered at maximal dosages. This definition has evolved with the development of new therapies and evidence-based data supporting treatment to lower BP goals. OBJECTIVE: To assess whether vitamin C and atorvastatin improve endothelial function and blood pressure control in subjects with resistant arterial hypertension and dyslipidemia. METHODS: Forty-eight hyperlipidemic subjects with RH (office systolic BP >140 mmHg and/or office diastolic BP >90 mmHg notwithstanding antihypertensive treatment with three medications in maximal doses) were randomized into three groups to receive additional medication for 8 weeks. Group VTC (n = 17)--mean 24 hour SBP 150.6 +/- 5.2 mmHg, DBP 86.1 +/- 3.3 mmHg, low density lipoprotein 158.1 +/- 24.5 mg/dl--received vitamin C 500 mg per day; Group ATR (n = 15)--mean 24 hour SBP 153.1 +/- 4.8 mmHg, DBP 87.1 +/- 6.7 mmHg, LDL 162.6 +/- 13.6 mg/dl--received atorvastatin 20 mg/day; and Group PLA (n = 16)--mean 24 hour SBP 151.1 +/- 7.4 mmHg, DBP 84.8 +/- 5.9 mmHg, LDL 156.7 +/- 26.1 mg/dl--received a placebo. High resolution ultrasound was used to calculate brachial artery flow-mediated dilation, and 24 hour ambulatory BP monitoring was performed at study entry and after 8 weeks. RESULTS: In the ATR group there were significant reductions of SBP (deltaSBP1-2: 13.7 +/- 5.6 mmHg, P 0.001), DBP (deltaDBP1-2: 7.8 +/- 5.7 mmHg, P 0.01), LDL (deltaLDL1-2: 67.7 +/- 28.3 mg/dl, P < 0.001) and improvement of brachial artery FMD (deltaFMD2-1: 4.2 +/- 2.6%). No significant changes in BP, LDL and FMD were observed in the other two groups. CONCLUSIONS: In subjects with RH and dyslipidemia, atorvastatin 20 mg/day compared to vitamin C 500 mg/day may help to achieve better BP control and improve endothelial function in a finite period. A larger trial is needed to assess the drug's efficacy in this population for longer periods.

Anticholesteremic Agents↗
PubMed1999

[Spectroscopic study on the structure and orientation of 1-hydroxyl-5-dodecyloxy-naphthalene LB films].

Ultraviolet-visible (UV-Vis), infrared transmission reflection absorption (RA) and ATR spectra were used to study the mono-and multi-layer Langmuir-Blodgett (LB) films of C12H25ONaph (1,5)OH at various temperatures to investigate dependencies of the aggregation and phase transitions on the number of monolayers. The UV-vis spectra of the LB films revealed that C12H25ONaph (1,5)OH forms aggregates in the LB film. From the temperature dependence of UV-vis absorption spectra, it is clear that the aggregate was gradually converted to monomer with the temperature increased. A comparison of the infrared transmission and ATR spectra reveals that the hydrocarbon chains were tilted considerably in the LB film.

English Abstract↗
PubMed2005

A novel 5' ATRX mutation with splicing consequences in acquired alpha thalassemia-myelodysplastic syndrome.

BACKGROUND AND OBJECTIVES: Acquired alpha thalassemia (hemoglobin H (HbH) disease) is a rare complication of neoplastic chronic myeloid disorders, especially myelodysplastic syndrome. Acquired HbH has recently been associated with mutations in an X-linked gene, ATRX, previously linked to inherited ATR-X syndrome (alpha thalassemia-retardation-X linked). DESIGN AND METHODS: A Swiss man with chronic myelomonocytic leukemia complicated by various autoimmune disorders and by strikingly microcytic, hypochromic anemia was analyzed for the presence of acquired HbH. After HbH detection, we sought an underlying genetic cause. We used denaturing high-performance liquid chromatography to screen for an ATRX mutation, and measured ATRX expression by reverse transcriptase polymerase chain reaction. RESULTS: The patient had 50% HbH-containing cells on supravital staining. Marrow karyotype and the alpha globin cluster were normal. A clonally-restricted ATRX point mutation was detected in the conserved splice donor motif in intron 4 (IVS 4 +2 T-->C). Plasmid vector cloning of patient ATRX cDNA demonstrated both exon 4 skipping and partial intron retention with activation of a cryptic splice site, both outcomes resulting in frameshifts with premature stop codon generation in exon 5 and near-decimation of ATRX expression in myeloid cells. Normal exon 6 alternative splicing was retained. INTERPRETATION AND CONCLUSIONS: Intronic ATRX mutations with splicing consequences, uncommon in inherited ATR-X syndrome because of their devastating effect on expression of functional protein, should be routinely sought when undertaking molecular analysis of acquired HbH disease. Detection of an acquired ATRX mutation can help support clonality in karyotypically normal ambiguous myeloid disorders with HbH.

5' Flanking Region↗
PubMed2005

[Novel infrared spectroscopy methods for clinical diagnosis of tumor].

In this paper, the authors have reviewed their investigation on the clinical detection of tumor tissues by infrared spectroscopy in recent ten years. Based on the comparison of different IR spectroscopic methods such as IR transmission spectroscopy, micro-IR spectroscopy etc, the authors found the good consistency of the results of ATR (attenuated total reglection) IR spectroscopic method with those of pathological biopsy. The authors have directly measured the IR spectra of frozen tissues stored in liquid nitrogen and freshly resected tissues, and have realized the measurement of tumor tissues in vito during the operation process using a specially designed IR spectrometer connected with a mid-IR fiberoptic with an ATR probe. The authors have investigated the malignant and normal tissues including parotid, esophagus, stomach, colon, liver, gallbladder, breast, thyroid etc. and compared with the pathological results. The accuracy of this novel IR detection method is more than 90%.

Humans↗
PubMed2006

Retinoids restore normal cyclic nucleotide sensitivity of mutant ion channels associated with cone dystrophy.

PURPOSE: To determine whether inhibition of cyclic nucleotide-gated (CNG) ion channels by retinoids might be useful in treating degenerative retinal diseases in which either the CNG channels are hypersensitive to 3',5'-cyclic guanosine monophosphate (cGMP) or the photoreceptor cGMP concentration is elevated. METHODS: Patch clamp (electrophysiological) methods were used to measure activation by cGMP of wild-type human cone (hCNGA3), mutant cone (hCNGA3-N471S), and wild-type bovine rod (bCNGA1) CNG channels heterologously expressed in Xenopus oocytes. Cyclic GMP-activated currents were measured in excised, inside-out membrane patches before and after treatment with either all-trans retinal (ATR) or all-trans C22 aldehyde, which is too long to fit into the chromophore binding pocket of opsin and therefore cannot activate the visual transduction cascade. RESULTS: At physiological cGMP concentrations, 150 nM ATR reduced the open probability of the mutant cone CNG channel by reducing its apparent cGMP affinity to that of the normal cone channel. Furthermore, all-trans C22 aldehyde similarly inhibited the mutant cone channel as well as normal rod and cone CNG channels. CONCLUSIONS: Our results raise the possibility that retinoids, such as all-trans C22 aldehyde, that inhibit CNG channels without affecting the transduction cascade, may be useful in treating degenerative retinal diseases in which either the cGMP concentration is elevated or the CNG channels are hypersensitive to cGMP.

Animals↗
PubMed1991

Aging of silastic peritoneal catheters.

Increasing the survival of patients on CAPD is related to the long-term reliability of the peritoneal access. Six silicone Tenckhoff catheters (with strip or diffuse barium sulphate inclusion) removed after 39-69 months because of the appearance of external segment fissures, were analysed by scanning electron microscopy (SEM) and infra-red spectroscopy with attenuated total refractance (ATR). The extracorporeal portion of the catheters showed (by ATR) a more prominent oxidation peak on the external than the internal surface; SEM showed marks and cracks on the external surface and exfoliation and flattening of the silastic reticle on the intraluminal surface. No evidence of oxidation was found in the intra-abdominal portion of the catheters but biofilm was found. We suggest that barium sulphate may render the silastic brittle and physiological and environmental long-term factors (such as uv-rays, temperature, sweat and disinfectants) could cause oxidation and loss of physico-chemical properties, with critical aging of the silastic and loss of catheter resistance to mechanical injury.

Adult↗