Identification of putative genetic modifying factors that influence the development of Papillon-Lefévre or Haim-Munk syndrome phenotypes.

BACKGROUND: Papillon-Lefévre syndrome (PLS; OMIM 245000) and Haim-Munk syndrome (HMS; OMIM 245010), which are both characterized by palmoplantar hyperkeratosis and periodontitis, are phenotypic variants of the same disease caused by mutations of the cathepsin C (CTSC) gene. AIM: To identify putative genetic modifying factors responsible for the differential development of the PLS or HMS phenotypes, we investigated two Hungarian patients with different phenotypic variants (PLS and HMS) but carrying the same homozygous nonsense CTSC mutation (c.748C/T; p.Arg250X). METHODS: To gain insights into phenotype-modifying associations, whole exome sequencing (WES) was performed for both patients, and the results were compared to identify potentially relevant genetic modifying factors. RESULTS: WES revealed two putative phenotype-modifying variants: (i) a missense mutation (rs34608771) of the SH2 domain containing 4A (SH2D4A) gene encoding an adaptor protein involved in intracellular signalling of cystatin F, a known inhibitor of the cathepsin protein, and (ii) a missense variant (rs55695858) of the odorant binding protein 2A (OBP2A) gene, influencing the function of the cathepsin protein through the glycosyltransferase 6 domain containing 1 (GLT6D1) protein. CONCLUSION: Our study contributes to the accumulating evidence supporting the clinical importance of phenotype-modifying genetic factors, which have high potential to aid the elucidation of genotype-phenotype correlations and disease prognosis.

The management and genetic background of pityriasis rubra pilaris: a single-centre experience.

BACKGROUND: Pityriasis rubra pilaris (PRP) is a rare chronic inflammatory dermatosis with multifactorial aetiology. It is known that particular caspase recruitment domain family member 14 (CARD14) gene mutations are associated with familial PRP and certain forms of psoriasis. Additionally, few data are available about the role of CARD14 gene variants in sporadic PRP. The clinical picture is variable for the different types of PRP, therefore choosing the adequate treatment is often difficult, furthermore there are no specific guidelines for therapy. OBJECTIVE: Our aim was to survey the efficacy of the applied therapies and to screen the CARD14 gene variants in our PRP patients. METHODS: In this retrospective study, patients diagnosed with PRP between 2006 and 2016 at our clinic were involved. Besides the follow-up study of the treatments, the genetic analysis of CARD14 gene was performed. RESULTS: We analysed 19 patients, among whom 17 were diagnosed with type I, one with type III, and one with type V PRP. The majority of the patients were successfully treated with acitretin in combination with systemic corticosteroids, and the remaining patients were treated with other systemic therapies with diverse effects. The genetic screening of CARD14 gene revealed two previously described mutations (rs114688446, rs117918077) and six polymorphisms (rs28674001, rs2066964, rs34367357, rs11653893, rs11652075, rs2289541). Ten of 19 patients carried different CARD14 genetic variants either alone or in combination. CONCLUSION: Based on our experience, we propose that acitretin and an initial combination of short-term systemic corticosteroid therapy could be a successful treatment option for PRP. Although we identified several CARD14 variants in almost half of our cases, we did not find a correlation between the therapeutic response and the genetic background. Our data support the previous observation that CARD14 genetic variants are not specific to PRP, although they may indicate chronic inflammation.

Atypical neurofibromatosis type 1 with unilateral limb hypertrophy mimicking overgrowth syndrome.

Neurofibromatosis type 1 (NF1; OMIM 162200), a dominantly inherited multitumor syndrome, results from mutations in the Neurofibromin 1 (NF1) gene. We present the case of a Hungarian woman with the clinical phenotype of NF1 over her whole body and the clinical features of unilateral overgrowth involving her entire left leg. This unusual phenotype suggested either the atypical form of NF1 or the coexistence of NF1 and overgrowth syndrome. Direct sequencing of the genomic DNA isolated from peripheral blood revealed a novel frameshift mutation (c.5727insT, p.V1909fsX1912) in the NF1 gene. Next-generation sequencing of 50 oncogenes and tumour suppressor genes, performed on the genomic DNAs isolated from tissue samples and peripheral blood, detected only wild-type sequences. Based on these results, we concluded that the patient is affected by an unusual phenotype of NF1, and that the observed unilateral overgrowth of the left leg might be a rare consequence of the identified c.5727insT mutation.

One mutation, two phenotypes: a single nonsense mutation of the CTSC gene causes two clinically distinct phenotypes.

BACKGROUND: Papillon-Lefévre syndrome (PLS; OMIM 245000) and Haim-Munk syndromes (HMS; OMIM 245010) are phenotypic variants of the same rare disease caused by mutations of the cathepsin C (CTSC) gene, and they exhibit autosomal recessive inheritance. AIMS: To identify diseases caused by mutations of the CTSC gene in two Hungarian patients and to perform haplotype analysis to elucidate any familial relationship between them. METHODS: Mutation screening and polymorphism analysis were performed by direct sequencing of the CTSC gene. RESULTS: Mutation screening of the CTSC gene from the two patients revealed the presence of the same homozygous nonsense mutation (c.748C/T; p.Arg250X). However, one patient exhibited the PLS phenotype and the other the HMS phenotype. Although these patients were not aware that they were related, haplotype analysis, especially the genotypes of the rs217116 and the rs217115 polymorphisms, clearly indicated that the patients carry the same haplotype, whereas the unrelated healthy controls carried several different haplotypes. CONCLUSIONS: Our results demonstrate that PLS and HMS are phenotypic variants of the same disease and, additionally, exclude the presence of a putative genetic modifier factor within the CTSC gene that is responsible for the development of the two phenotypes. We suggest that this putative genetic modifier factor is located outside the CTSC gene, or alternatively, that the development of the different phenotypes is the consequence of different environmental or lifestyle factors.

Bile acids inhibit Na⁺/H⁺ exchanger and Cl⁻/HCO3⁻ exchanger activities via cellular energy breakdown and Ca²âº overload in human colonic crypts.

Bile acids play important physiological role in the solubilisation and absorption of dietary lipids. However, under pathophysiological conditions, such as short bowel syndrome, they can reach the colon in high concentrations inducing diarrhoea. In this study, our aim was to characterise the cellular pathomechanism of bile-induced diarrhoea using human samples. Colonic crypts were isolated from biopsies of patients (controls with negative colonoscopic findings) and of cholecystectomised/ileum-resected patients with or without diarrhoea. In vitro measurement of the transporter activities revealed impaired Na⁺/H⁺ exchanger (NHE) and Cl⁻/HCO3⁻ exchanger (CBE) activities in cholecystectomised/ileum-resected patients suffering from diarrhoea, compared to control patients. Acute treatment of colonic crypts with 0.3 mM chenodeoxycholate caused dose-dependent intracellular acidosis; moreover, the activities of acid/base transporters (NHE and CBE) were strongly impaired. This concentration of chenodeoxycholate did not cause morphological changes in colonic epithelial cells, although significantly reduced the intracellular ATP level, decreased mitochondrial transmembrane potential and caused sustained intracellular Ca²âº elevation. We also showed that chenodeoxycholate induced Ca²âº release from the endoplasmic reticulum and extracellular Ca²âº influx contributing to the Ca²âº elevation. Importantly, our results suggest that the chenodeoxycholate-induced inhibition of NHE activities was ATP-dependent, whereas the inhibition of CBE activity was mediated by the sustained Ca²âº elevation. We suggest that bile acids inhibit the function of ion transporters via cellular energy breakdown and Ca²âº overload in human colonic epithelial cells, which can reduce fluid and electrolyte absorption in the colon and promote the development of diarrhea.

Trends in Major Lower Limb Amputation Related to Peripheral Arterial Disease in Hungary: A Nationwide Study (2004-2012).

OBJECTIVES: To assess the trends of peripheral arterial disease associated major lower limb amputation in Hungary over a 9 year period (2004-2012) in the whole Hungarian population. METHODS: This was a retrospective cohort study employing administrative health care data. Major amputations were identified in the entire Hungarian population during a 9 year period (2004-2012) using the health care administrative data. Direct standardization was used to eliminate the potential bias induced by the different age and sex structure of the compared populations. For external direct standardization, the ESP 2013 was chosen as reference. RESULTS: 76,798 lower limb amputations were performed. The number of major amputations was 38,200; these procedures affected 32,084 patients. According to case detection, 50.4% of the amputees were diabetic. The overall primary amputation rate was 71.5%. The annual crude and age adjusted major amputation rates exhibited no significant long-term pattern over the observation period. The major lower limb amputation incidence for the overall period was 42.3/10(5) in the total population and 317.9/10(5) in diabetic population. CONCLUSION: According to this whole population based study from Hungary, the incidence of lower limb major amputation is high with no change over the past 9 years. An explanation for this remains to be determined, as the traditional risk factors in Hungary do not account for it. The characteristics of major amputation (the rate of primary amputation, the ratio of below to above knee amputation and the age of the affected population) underline the importance of screening, early detection, improved vascular care and an optimal revascularization policy. Standardization and validation of amputation detection methods and reporting is essential.

Serological responses to Cryptosporidium antigens in inhabitants of Hungary using conventionally filtered surface water and riverbank filtered drinking water.

In this study the putative protective seroprevalence (PPS) of IgG antibodies to the 27-kDa and 15/17-kDa Cryptosporidium antigens in sera of healthy participants who were and were not exposed to Cryptosporidium oocysts via surface water-derived drinking water was compared. The participants completed a questionnaire regarding risk factors that have been shown to be associated with infection. The PPS was significantly greater (49-61%) in settlements where the drinking water originated from surface water, than in the control city where riverbank filtration was used (21% and 23%). Logistic regression analysis on the risk factors showed an association between bathing/swimming in outdoor pools and antibody responses to the 15/17-kDa antigen complex. Hence the elevated responses were most likely due to the use of contaminated water. Results indicate that waterborne Cryptosporidium infections occur more frequently than reported but may derive from multiple sources.

City-wide wastewater genomic surveillance through the successive emergence of SARS-CoV-2 Alpha and Delta variants.

Genomic surveillance of SARS-CoV-2 has provided a critical evidence base for public health decisions throughout the pandemic. Sequencing data from clinical cases has helped to understand disease transmission and the spread of novel variants. Genomic wastewater surveillance can offer important, complementary information by providing frequency estimates of all variants circulating in a population without sampling biases. Here we show that genomic SARS-CoV-2 wastewater surveillance can detect fine-scale differences within urban centres, specifically within the city of Liverpool, UK, during the emergence of Alpha and Delta variants between November 2020 and June 2021. Furthermore, wastewater and clinical sequencing match well in the estimated timing of new variant rises and the first detection of a new variant in a given area may occur in either clinical or wastewater samples. The study's main limitation was sample quality when infection prevalence was low in spring 2021, resulting in a lower resolution of the rise of the Delta variant compared to the rise of the Alpha variant in the previous winter. The correspondence between wastewater and clinical variant frequencies demonstrates the reliability of wastewater surveillance. However, discrepancies in the first detection of the Alpha variant between the two approaches highlight that wastewater monitoring can also capture missing information, possibly resulting from asymptomatic cases or communities less engaged with testing programmes, as found by a simultaneous surge testing effort across the city.

The effect of laparoscopic pre- and postconditioning on pneumoperitoneum induced injury of the peritoneum.

INTRODUCTION: Pneumoperitoneum, widely used in laparoscopic surgery increases the intraabdominal pressure, leading to hypoperfusion of the abdominal organs, and promoting the buildup of reactive oxygen species(ROS) and inflammatory cytokines which in turn impairs the body postoperatively. Aim of our investigation was to evaluate the potential protective effects of short ischemic episodes on ischemic damages. METHODS: 70 Wistar rats were used, divided into 7 groups: 1st group sham, 2nd group pneumoperitoneum with 5 mmHg, 3rd group preconditioning with 5 mmHg, 4th group: postconditioning with 5 mmHg, 5th group pneumoperitoneum with 10 mmHg, 6th group: preconditioning with 10 mmHg, 7th group postconditioning with 10 mmHg. Pneumoperitoneum was created by Veres needle. Oxidative stress parameters: malondialdehyde (MDA) concentration, reduced glutathione (GSH), sulfhydril (SH-), myeloperoxidase (MPO) levels and superoxide-dismutase (SOD) activity were measured. We measured TNF-α and IL-6 concentrations. We monitored the activation of anti- and proapoptotic common signaling pathways (bax, bcl-2, p53) during the early phase of reperfusion. Histology was made from kidney samples. RESULTS: GSH concentrations were significantly reduced, MDA concentrations were significantly higher in each group compared to the Sham. SOD enzyme: a pressure of 10 mmHg elicited significantly greater damage than 5 mmHg. There was a significantly higher SOD activity in group 10 mmHg IPC compared to 10 mmHg. We found that the expression of bax was considerably higher in the none conditioned groups. Noticeably higher expression of anti-apoptotic bcl-2 level was measured in 10 mmHg IPC and 10 mmHg IPoC groups. In case of p53 expression: significant decrease could be seen in groups 10 mmHg IPC and 10 mmHg IPoC compared to the 10 mmHg group. CONCLUSION: Based on our results, the elevated intraabdominal pressure due to pneumoperitoneum induces oxidative stress, which is dependent on the applied pressure. Mostly precondiotioning - but also postconditioning - reduces surgical stress following laparoscopic procedures. In order to explore its mechanism it requires further investigations.

The significance of micro- and macrovascular biomarkers on cardiovascular outcome in chronic kidney disease: a prospective cohort study.

Measures of small and large artery dysfunction have not been investigated in a single cohort for the prediction of cardiovascular (CV) events in patients with nondialysed (ND) chronic kidney disease (CKD). This prospective cohort study aimed to determine whether central pulse wave velocity (cPWV), central pulse pressure (CPP) or microvascular post-occlusive reactive hyperaemia area (PORHHA) independently predict CV events and mortality in CKD-ND. A total of 94 stage 1-5 CKD-ND (65.3±13.1 years; estimated glomerular filtration rate 35.3 (22.8-49.4) ml min(-1) per 1.73 m(2)) patients were followed-up for a median of 52 (36-65) months and had baseline cPWV and CPP measured by applanation tonometry and PORHHA by laser Doppler flowmetry. Multiple failure time Cox regression models were used to determine the predictive role of vascular parameters on CV mortality and events. Based on multiple linear regressions, baseline age, diabetes, CV disease, and systolic blood pressure (SBP) were independently related to cPWV (R(2)=0.3), SBP and PORHHA to CPP (R(2)=0.45), whereas CPP was the only parameter independently related to PORHHA (R(2)=0.16, all P<0.05). During follow-up, 41 CV events occurred (14 CV deaths). In univariate analyses, cPWV (1.07 (1.02-1.13) per m s(-1)), CPP (1.04 (1.01-1.07) per mm Hg) and lnPORHHA (0.70 (0.58-0.85) per ln(PU × s)) were all related to the outcome. Baseline diabetes (HR 3.07 (1.65-5.68)), lnFGF23 (fibroblast growth factor-23; 1.86 (1.13-3.06) per RU ml(-1)) and CPP (1.04 (1.01-1.07) per mm Hg) were independent predictors of CV events. The impaired pulsatile component of large arteries (CPP) independently of other vascular markers (cPWV, PORHHA) predicted CV outcomes in CKD-ND. CPP may integrate the information provided by cPWV and PORHHA.

The transfer of docosahexaenoic acid from the yolk to the tissues of the chick embryo.

Changes in the amounts of the major fatty acids present in the lipids of the yolk complex and the embryo were delineated during embryogenesis of the chicken. The rates of transfer of palmitic, oleic, linoleic, linolenic and arachidonic acids from the lipids of the yolk complex were essentially identical. In contrast, docosahexaenoic acid (DHA) was preferentially transferred from the yolk complex at a rate which was significantly higher than that exhibited by the other major fatty acids. The rates of accumulation of both arachidonic acid and DHA in the lipids of the whole embryo were significantly greater than the rates observed for the C16 and C18 fatty acids, particularly between days 12 and 16 of the 21-day embryonic period. Analysis of the fatty acid composition of plasma lipid throughout development indicated that the triacylglycerol fraction contained relatively high proportions (up to approx. 14% w/w of total fatty acids) of DHA, but much lower proportions (approx. 3%) of arachidonic acid. In contrast, plasma phospholipid was enriched in arachidonic acid (up to approx. 18%), but contained much lower proportions (generally less than 3%) of DHA. A considerable amount of DHA was incorporated into adipose tissue triacylglycerol, so that by the time of hatching, the tissue represented a major store of this fatty acid. Over the hatching period, the amount of DHA in adipose triacylglycerol decreased dramatically, by up to 85%, whereas there was little or no change in the amounts of the other major fatty acyl components in this tissue. The amount of DHA as a component of brain phospholipid increased continuously throughout the developmental period studied. However, by the time of hatching, the amount of DHA in brain phospholipid represented less than 10% of the amount of this fatty acid originally present in the lipids of the yolk.

Bilateral axillobrachial and external carotid artery manifestation of giant cell arteritis: important role of color duplex ultrasonography in the diagnosis.

A 76-year-old man was admitted to our hospital with vertigo. Previously he had been extensively examined because of an increased erythrocyte sedimentation rate without any clinical symptoms. Physical examination revealed 60 mmHg blood pressure difference between the two arms. Color duplex ultrasound examination revealed bilateral extreme narrowing of the external carotid and axillobrachial artery with a dark, hypo-echoic halo around the lumen. This condition was recognized as a specific sign for giant cell arteritis (GCA), described originally in cases of temporal arteritis. The diagnosis was confirmed by biopsy of the temporal artery. In contrast to the typical cranial form of GCA -- our patient showed an unusual, bilateral large-vessel manifestation. The diagnosis was based on ultrasound images rather than on symptoms that characterize the well-known temporal form. This observation emphasizes the role of color duplex ultrasonography in the diagnosis and follow-up of GCA.

Day-night blood pressure variation in normotensive and hypertensive NIDDM patients with asymptomatic autonomic neuropathy.

In order to assess the characteristics of day-night blood pressure (BP) variation in normotensive and hypertensive non-insulin-dependent diabetic (NIDDM) patients with asymptomatic autonomic neuropathy, 54 NIDDM patients and 13 healthy control subjects were studied by casual BP measurements and 24-h ambulatory blood pressure monitoring. Signs but not symptoms of autonomic neuropathy were documented by results of standard cardiovascular function tests in each patient. Daytime (06:00-22:00) and nighttime (22:00-06:00) BP values were separately analyzed and delta day-night BP values and diurnal index were determined. Patients were classified as being normotensive or having hypertension according to the casual BP values and medical history. In normotensive NIDDM patients (n = 30), nighttime systolic BP was significantly higher, whereas delta day-night systolic and delta day night diastolic BP values as well as diurnal index were considerably lower than those in control subjects (n = 13). In hypertensive NIDDM patients (n = 24), similar alterations were found at higher BP levels. No significant difference was found in BP values if normoalbuminuric and microalbuminuric NIDDM patients were compared. 'Non-dipper' phenomenon could be found in normotensive and hypertensive NIDDM patients with asymptomatic autonomic neuropathy, suggesting that relative sympathetic overdrive due to incipient and predominantly parasympathetic impairment of cardiovascular innervation might play a role in early alterations of circadian BP variation.

Impairment of the NO/cGMP pathway in the fasting and postprandial state in type 1 diabetes mellitus.

The assessment of the postprandial state in diabetes mellitus has gained importance due to postprandial hyperglycemia being considered as an independent risk factor for cardiovascular disease. Hyperglycemia may contribute to vascular dysfunction through the alteration of the nitric oxide/cyclic guanosine monophosphate (NO/cGMP) pathway. The authors assessed the NO/cGMP pathway in the fasting and postprandial state in 20 type 1 diabetic patients (age: 34.1 +/- 2.6 years, body mass index (BMI): 24.1 +/- 1.3 kg/m (2), duration of diabetes: 16 +/- 2.2 years, HbA (1C): 8.3 +/- 0.4 %, [x +/- SEM], 10 without, 10 with late complications) and 20 matched control subjects (age: 39.7 +/- 1.9 years, BMI: 25.3 +/- 1.1 kg/m (2)). In the fasting state NO end product (nitrite/nitrate) levels did not differ between the diabetic and control group, cGMP levels were found to be significantly lower in the diabetic group (2.5 +/- 0.2 vs. 4.6 +/- 0.6 nmol/l, p = 0.01). A higher level of lipid peroxidation end products (TBARS) was found in diabetic subjects (6.7 +/- 0.4 vs. 5.0 +/- 0.3 micro mol/l, p = 0.004). The diabetic subgroup without late complications had significantly higher nitrite/nitrate levels compared to the patients with complications (57.8 +/- 6.6 vs. 30.4 +/- 4.3 micro mol/l, p = 0.006), their TBARS and cGMP levels were similar. The control subjects responded to the test meal with an increase in the cGMP levels (4.6 +/- 0.6 to 5.5 +/- 0.6 nmol/l, p = 0.02), while in the diabetic group no change was detected. Postprandial nitrite/nitrate levels decreased in both groups, they were significantly lower in the diabetic group. There was no difference between postprandial nitrite/nitrate, cGMP, or glucose levels in the diabetic subgroups. Postprandial glucose levels showed a significant negative correlation with cGMP levels in the diabetic group (r = - 0.50, p = 0.02). The results suggest that in subjects with type 1 diabetes mellitus NO might have an impaired ability to induce cGMP production in the fasting state prior to the development of late specific complications or microalbuminuria under hyperglycemic conditions. Postprandial hyperglycemia is suggested to interfere with endothelial NO action, as shown by the decreased nitrite/nitrate and unchanged cGMP plasma levels in the diabetic group. The impairment of the NO/cGMP pathway both in the fasting and postprandial state that was shown in patients without diabetic complications may be an early sign of hyperglycemia induced vascular damage in type 1 diabetes mellitus.

Neurobehavioral outcomes of cocaine-exposed infants.

The present study investigated the neurobehavioral outcomes of fetal cocaine exposure. Attempts were made to control, by design or statistical analysis, for significant confounders. Timing and amount of drug exposures were considered, and biologic measures of exposure were quantified to classify exposure severity. One hundred sixty-one non-cocaine and 158 cocaine-exposed (82 heavily and 76 lightly exposed) infants were seen at a mean-corrected age of 43 weeks post-conception and administered the Neurobehavioral Assessment (NB Assessment). Heavily cocaine-exposed infants had more jitteriness and attentional problems than lightly and non-exposed infants. They also had more movement and tone abnormalities, and sensory asymmetries than non-exposed infants. Heavily exposed infants were more likely to be identified with an abnormality than non-exposed infants and there was a trend toward heavily exposed infants being more likely to be identified with an abnormality than lightly exposed infants. Furthermore, there was a trend for heavily exposed infants to be less likely to be testable than non-exposed infants. After the confounding and mediating factors were considered, heavily cocaine-exposed infants were four times as likely to be jittery and nearly twice as likely to demonstrate any abnormality than lightly and non-exposed infants, but all other effects were no longer significant. Higher concentrations of the cocaine metabolites of cocaine, cocaethylene, and benzoylecgonine (BZE) were related to higher incidence of movement and tone abnormalities, jitteriness, and presence of any abnormality. Higher cocaethylene levels were related to attentional abnormalities and higher meta-hydroxybenzoylecgonine (m-OH-BZE) was related to jitteriness. Drug effects on attention were mediated by maternal psychological distress, suggesting that this factor should be considered in future studies of drug exposure effects.

Cold pressor test and plasma endothelin-1 concentration in primary open-angle and capsular glaucoma.

PURPOSE: The authors investigate cutaneous capillary blood flow using the cold pressor test and plasma endothelin-1 (ET-1) concentration in primary open-angle glaucoma (POAG) and capsular glaucoma (CG), and evaluate the connection between the two factors, which reflect vasoconstrictive mechanisms with a potential role in the pathogenesis of glaucoma. METHODS: The ET-1 concentration of venous blood plasma samples from 20 patients with POAG, 22 patients with CG, and 44 healthy volunteers was measured using a radioimmunoassay kit. On a separate occasion, the right hand was subjected to the cold pressor test (hand immersed in 4 degrees C water for 30 seconds, then in 30 degrees C water for 2 minutes), during which cutaneous capillary blood flow of the left middle finger was measured using a Periflux 4001 Master Laser Doppler Flowmeter (Perimed AB, Järfälla, Sweden). RESULTS: In the CG group, baseline cutaneous capillary blood flow was significantly lower than either that of POAG (p = 0.001) or that of the healthy group (p = 0.046). In the CG group, time to maximal cold-induced flow reduction was significantly longer than in the POAG group (p = 0.028) or in the healthy group (p = 0.025). Also, recovery time was significantly longer in CG than in the healthy group (p = 0.008) and tended to be longer than in the POAG group. No statistically significant difference between the groups was found either in the frequency of increased vasospastic response (cold-induced flow reduction higher than 70% of the baseline value) or in ET-1 concentration. No correlation was seen between ET-1 concentration and the findings of the cold pressor test. CONCLUSION: The results suggest that in CG, which is a systemic disease with vascular abnormalities, baseline cutaneous capillary perfusion and its response to cold and warmth are altered, without any alteration of plasma ET-1 level. The authors found that both plasma ET-1 level and the response to the cold pressor test are normal in patients with POAG. These findings suggest that regulation of cutaneous capillary perfusion and the concentration of plasma ET-1 are not related to each other in patients with glaucoma.

Developmental changes in the levels of molecular species of triacylglycerol that contain docosahexaenoic acid in adipose tissue of the chick embryo.

Triacylglycerols from the initial yolk and from the adipose tissue of the chick embryo were subjected high-performance liquid chromatography in the silver ion mode to resolve molecular species of triacylglycerol on the basis of the degree of unsaturation. A total of 12 such species was resolved from the yolk samples, with only one of these species containing docosahexaenoic acid. In contrast, 17 species were resolved from adipose tissue at day 12 of embryo development, of which 8 contained docosahexaenoic acid. The major species containing this fatty acid consisted of docosahexaenoic acid in combination with palmitic and oleic acids. The amounts of the species consisting of C16 and C18 fatty acids in the adipose tissue increased continuously from day 12 until just before hatching at day 19 and then decreased slightly over the hatching period. In contrast, the amounts within the adipose depot of the species containing docosahexaenoic acid reached a maximal level by day 16 and then decreased dramatically to almost undetectable levels during the hatching period. The possibility that adipose tissue triacylglycerol in the chick embryo may function as a temporary store of docosahexaenoic acid for subsequent delivery to the developing neural tissues is suggested.