Cutaneous Hyperemia Research Articles

Effect of home-based heat therapy on 24-h blood pressure and cutaneous microvascular function in post-menopausal women with hypertension

Hypertension is a leading risk factor for cardiovascular morbidity and mortality and is often accompanied by microvascular dysfunction. Despite a clear effcacy in men, standard antihypertensive medications are less effective in post-menopausal women. Consequently, adjuvant therapies are needed to improve blood pressure control and microvascular function in post-menopausal women. Heat therapy may fill this therapeutic gap as it has been shown to reduce blood pressure and improve microvascular function in healthy and certain clinical populations. Therefore, the purpose of this study was to test the hypothesis that 8 weeks of home-based heat therapy would improve 24-h blood pressure and cutaneous nitric oxide-dependent vasodilation in post-menopausal women with hypertension. Post-menopausal women (69 ± 5 y) with hypertension were randomized to 8 weeks of sham ( N = 15) or heat therapy ( N = 13). Participants immersed their lower legs ~33 cm into a circulated and temperature-controlled (sham: 35 °C; heat therapy: 42 °C) water bath 4 days per week, and 45 min per session. Blood pressure and cutaneous microvascular function and were assessed before (pre) and after (post) the 8-week intervention. Mean arterial blood pressure was measured across 24-h using an ambulatory monitor. To assess microvascular function, an intradermal microdialysis probe was inserted in the anterior aspect of the lower leg at a site directly exposed to water (immersed) and at another site not directly exposed (non-immersed). Red blood cell flux was measured (laser doppler flowmetry) during cutaneous hyperemia induced by 39 °C local heating. N(G)-nitro-L-arginine methyl ester (L-NAME; 20mM) was then infused in each probe until a nadir in red blood cell flux was achieved. Cutaneous vascular conductance was calculated as red blood cell flux divided by mean arterial pressure and normalized to maximal vasodilation (42 °C heating + 56 mM sodium nitroprusside; CVC%max). Nitric oxide-dependent dilation was calculated as the difference between CVC%max measured during the 39 °C plateau and the L-NAME nadir. Mean arterial blood pressure did not differ across time or between groups (sham: pre, 96 ± 5 mmHg vs. post, 96 ± 6 mmHg; heat therapy: pre, 97 ± 4 mmHg vs. 99 ± 7 mmHg; P = 0.5 for interaction). Cutaneous vasodilation induced by local heating did not differ across time for either group (sham: pre, 60 ± 19 CVC%max vs. post, 64 ± 12 CVC%max; heat therapy: pre, 68 ± 15 CVC%max vs. post, 63 ± 13 CVC%max) or between immersed and non-immersed sites ( P = 0.9 for interaction). Similarly, nitric oxide-dependent vasodilation did not differ across time or between sites for either group ( P = 1.0 for interaction). Taken together, 8 weeks of home-based heat therapy does not improve blood pressure or cutaneous microvascular function in post-menopausal women with hypertension. This work was supported by grants from the National Institutes of Health (T32 AG020494; R01AG059314; F32HL167556) and the American Heart Association (TPA958179). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Heat ameliorative effects of rumen protected niacin supplementation in lactating Surti buffaloes

Niacin may cause evaporative thermolysis through cutaneous hyperemia, vasodilation, increased sweating rate and decreased skin temperature. It is antilipolytic and can improve metabolic responses. Heat stress ameliorative effects of rumen protected niacin (RPN) supplementation in lactating Surti buffaloes during summer has been investigated in present study. Fourteen lactating Surti buffaloes were divided into two groups (Control-T1, N=7; RPN-T2, N=7). T2 (RPN) group was supplemented with RPN 6 g/ animal/ day in two divided dose for 4 weeks. Meteorological, physiological, sweating rate and skin temperature parameters, milk yield and composition were recorded at weekly intervals. Hematological and biochemical analytes were analyzed at week 1 and 4. RPN supplementation decreased physiological parameters RT, RR and TT; increased (P≤0.05) sweating rate and decreased (P≤0.05) skin surface temperature; increased (P≤0.05) TEC, Hb, HCT, LYM and decreased (P≤0.05) GRAN in hematological profile; increased (P≤0.05) glucose and decreased (P≤0.05) cholesterol, triglyceride, NEFA and BHB among biochemical metabolites and increased (P≤0.05) GSH and SOD and decreased (P≤0.05) LPO in oxidative stress profile. RPN supplementation increased milk yield and milk fat. It was concluded that supplementation of rumen protected niacin in lactating Surti buffaloes increases sweating rate, reduces oxidative stress and increases milk fat and milk production.

Global Reach 2018: Nitric oxide-mediated cutaneous vasodilation is reduced in chronic, but not acute, hypoxia independently of enzymatic superoxide formation

We tested the hypotheses that 1) cutaneous microvascular function is impaired by acute normobaric and chronic hypobaric hypoxia and 2) that the superoxide free radical (via NADPH oxidase or xanthine oxidase) contributes to this impairment via nitric oxide (NO) scavenging. Local heating-induced cutaneous hyperemia (39 °C) was measured in the forearm of 11 male lowlanders at sea level (SL) and following 14–18 days at high altitude (HA; 4340 m in Cerro de Pasco, Peru), and compared to 11 highlanders residing permanently at this elevation. Cutaneous vascular conductance (CVC; laser-Doppler flux/mean arterial pressure) was not different during 39 °C [control site: 73 (19) vs. 71 (18)%max; P = 0.68] between normoxia and acute normobaric hypoxia (FIO2 = 0.125; equivalent to HA), respectively. At HA, CVC was reduced during 39 °C in lowlanders compared to SL [control site: 54 (14) vs. 73 (19)%max; P < 0.01] and was lower in Andean highlanders compared to lowlanders at HA [control site: 50 (24) vs. 54 (14)%max; P = 0.02]. The NO contribution to vasodilation during 39 °C (i.e., effect of NO synthase inhibition) was reduced in lowlanders at HA compared to SL [control site: 41 (11) vs 49 (10)%max; P = 0.04] and in Andean highlanders compared to lowlanders at HA [control site: 32 (21) vs. 41 (11)%max; P = 0.01]. Intradermal administration (cutaneous microdialysis) of the superoxide mimetic Tempol, inhibition of xanthine oxidase (via allopurinol), or NADPH oxidase (via apocynin) had no influence on cutaneous endothelium-dependent dilation during any of the conditions (all main effects of drug P > 0.05). These results suggest that time at HA impairs NO-mediated cutaneous vasodilation independent of enzymatic superoxide formation.

Carp edema virus-related mortality in wild adult common carp (cyprinus carpio) in Italy.

Mortality in wild fish populations represents a challenging issue for public fish health inspectors. When a single fish species is involved, an infective aetiology is frequently suspected, with focus on viral notifiable diseases. However, other viral agents not subjected to regulation and causing mortality in common carp have been reported such as carp edema virus (CEV). In mid-June 2020, a severe common carp mortality was observed in an artificial lake in north-east of Italy. Sleepy fish were noted some days before the beginning of the mortality itself, which lasted several days and involved over 340 adult specimens. During the outbreak, water temperature was around 15°C, water quality was normal, and no adverse meteorological events were reported in the area. Four specimens, which showed severe cutaneous hyperaemia and increased mucus production on skin and gills, were tested by bacteriological methods and virological analysis targeting the main carp pathogens. Molecular analysis performed on gills, kidney and brains from all the fish analysed resulted positive for CEV, which, based on anamnestic information and laboratory findings, was considered the responsible for the mortality event herein described.

Pathological and mortality findings associated withAeromonas hydrophilafrom frog eggs in Al‐Ahsa region of Saudi Arabia

Background Amphibians decline globally due to infection with virulent bacteria, despite their vital roles in the ecosystem. The current study aimed at addressing the pathological and bacterial findings of the infected Pelophylax ridibundus indigenous to the Al-Ahsa region. Many clinical signs were observed in the eggs, including discoloration, disintegration of the outer jelly coat; defects in morphology, and mortality were reported. Furthermore, neuromasts lacking apical cilia and microvilli were observed in the cleavage stages of the infected developing egg. Additionally, cutaneous hyperaemia, lethargy, peripheral oedema, subcutaneous haemorrhage and cutaneous ulcerations were observed in the infected P. ridibundus adults. Methods Ribbons of frog eggs were collected from Al-Ahsa oasis, the Eastern region, Kingdom of Saudi Arabia (KSA), and examined under light and scanning electron microscope. The developed eggs and adults were further examined using a dissecting microscope to determine signs of infection. A bacterial strain designated as PRE-1 was isolated from the infected eggs, identified genotypically and then characterized phenotypically. Strain PRE-1 was identified as Aeromonas hydrophila based on the comparative gene sequences of the 16S rRNA gene at identity level of (99.92%). Furthermore, phylogenetic relationship based on the 16S rRNA gene sequences of our strain and other relevant strains Aeromonas spp. showed that PRE-1 formed a cluster with A. hydrophila (99% bootstrap support), providing a robustness to the identification of PRE-1 as A. hydrophila. This bacterium was found to be associated with disease outbursts in the marsh frogs from the Al-Ahsa region. Conclusion It is important to continue monitoring the emerging diseases so that their cause can be discerned, and appropriate protocols can be applied to limit the spread of the loss of amphibians, which are vital for our ecosystem.

Atypical manifestation of Ichthyosis vulgaris in children: case report

Introduction: Ichthyosis vulgaris is a common disorder characterized clinically by xerosis, excessive scaling, hyperkeratosis, keratosis pilaris, palmar and plantar hyperlinearity. It is an autosomal dominant genetic disorder with a strong association to atopic disorders. Clinical manifestations typically begin in the first year of life, with a slight thickening of the skins surface and fine scaling, mainly on extensor areas of the extremities, scalp, central part of the face and buttocks. Flexion surfaces are not compromised, and the abdomen, neck, and face are rarely affected. Most cases are not severe, and their clinical manifestations may improve or even disappear with age. Objective: This study aims to discuss the abnormal clinical manifestations of the patient in relation to the characteristics of the disease. Case Report: Male patient, two years old, from São João da Boa Vista - SP, is the first gestation of a non-consanguineous couple without intercurrences in relation to the gestational antecedents; has no siblings. He had prenatal care, born cesarean delivery, at term, newborn suitable for gestational age weighed 3,140kg, 50th percentile, measured 49cm, cephalic perimeter 35cm, thoracic perimeter 33cm, Apgar 9/10. At birth, extremely dry skin was seen with fine, diffuse scaling. At fifteen days of life there was worsening of skin dryness along with widespread erythema of diffuse on his body, including the scalp, face and folds, uncommon manifestations in this pathology. With dermatological guidance, he started treatment with a 10% urea-based moisturizer with partial improvement of the cutaneous condition. At 6 months of age, when breastfeeding stopped, and milk formula was introduced, there was a significant worsening of the skin peeling, being laminar in the upper extremities, lower extremities, scalp, buttocks, abdomen and face. Along with this, he presented pruritus and severe cutaneous hyperemia. This initiated the use of highly hydrolyzed dairy formula, second generation antihistamine and maintenance of cutaneous hydration. Research was conducted for food allergies using RAST to test for major food antigens, the results were negative. Biopsy results were compatible with ichthyosis vulgar. The oral challenge test results were positive for proteins in cows milk. In a follow-up with allergist and dermatologist, the child began to maintain a diet that excludes cow’s milk and derivatives, along with industrialized products with dyes and preservatives that also worsen the cutaneous condition. At two years of age, he reports improvement in the appearance of the skin with less flaking and less pruritus present in exposed areas such as face, scalp and limbs. Also, he shows ephemeral episodes of skin whitening. Mother relates clinical cutaneous improvement with less sun exposure. His neuropsychomotor development is normal. He is currently using an antihistamine, 10% urea-based moisturizing liquid petroleum jelly and sunscreen. At his physical examination: weight and height z score 0. Fine scaling was seen in the abdomen and in plaques in the upper limbs and scalp. This is causing large, square, brown, adherent scales in the center, with loose edges and areas of scaling with erythematous fundus. There is slight alopecia in areas on the scalp.

Evidence of Racial Differences in Microvascular Function Among College-Aged Women

Microvascular dysfunction contributes to the development of hypertension and insulin resistance. The black population is at an elevated risk of both conditions relative to other racial groups. Previous studies indicate that college-aged black men, compared to their white counterparts, exhibit impaired microvascular function as assessed by post- occlusion reactive hyperemia (RH). It is unknown whether this racial disparity is present in healthy, young adult black (BW) and white women (WW). Furthermore, whether nitric oxide-mediated cutaneous microvascular hyperemia during local heating (LH) is different in these populations has not been determined. PURPOSE: The purpose of this study was to test the hypothesis that college-aged BW exhibit blunted RH and attenuated LH induced cutaneous hyperemia compared to age-matched WW. METHODS: College-aged BW (n=7) and WW (n=7) were studied during the early follicular phase of the menstrual cycle. For RH, brachial artery diameter and blood velocity were measured via Doppler ultrasound before and after 5 min of forearm occlusion. For LH, a microdialysis membrane was inserted in the dermis of the forearm and perfused with Ringer’s solution. Red blood cell flux was assessed with laser Doppler after ~40 min of continuous 39°C LH. Maximal flux was established with 28 mM sodium nitroprusside infusion and 43°C LH. Brachial BP was measured throughout the protocol and cutaneous vascular conductance (CVC) was calculated as flux / MAP and reported as % of max CVC. RESULTS: WW and BW were matched for age (21 ± 3 vs 20 ± 1 y, P = 0.58) and BMI (23 ± 2 vs 23 ± 3 kg/m2, P = 0.94). There were no differences between WW and BW in baseline blood velocity (23.1 ± 5.7 vs 24.4 ± 11.6 cm/s, P = 0.79) or blood flow (98.9 ± 38.3 vs 114.5 ± 80.7 ml/min, P = 0.65). WW and BW also had similar peak blood velocity (109.2 ± 13.8 vs 109.7 ± 28 cm/s, P = 0.97), peak blood flow (453.7 ± 164.7 vs 482.5 ± 187.7 ml/min, P = 0.77), and total blood flow AUC during the 120 s after cuff release (487.4 ± 178.5 vs 486.8 ± 190.1 ml, P = 0.99). However, compared to WW, BW had a significantly blunted CVC during 39°C LH (66 ± 17 vs 45 ± 10 %max, P = 0.02). CONCLUSIONS: BW had blunted blood flow responses to LH compared to WW despite similar blood velocity and flow responses during RH. This suggests that LH is more sensitive than RH to early impairments in microvascular function.

Impairment of microcirculation and vascular responsiveness in adolescents with primary Raynaud phenomenon

Background Raynaud’s phenomenon (RP) is a functional vascular disease, presenting with recurrent episodes of ischemia of extremities in response to cold and emotional stress. Investigating cutaneous microcirculation is an important tool in understanding the complex neuro-immuno-vascular interactions in its pathophysiological mechanisms. Since there is no available data on vascular responsiveness in RP in the paediatric population, we investigated skin perfusion and heat-induced hyperaemia in comparison with clinical severity and laboratory parameters of the disease.MethodsFifty two adolescents (27 patients with primary RP and 25 age-matched healthy controls) were investigated in the study. Patients were divided into two groups according to the symptoms existing within the previous 2 months. Following baseline microcirculation measurement with Laser Doppler flowmetry (Periflux 5000 system), all subjects underwent local heating test at 42 °C and 44 °C. Besides routine laboratory parameters, immune-serological tests and the vasoactive sensory neuropeptides somatostatin and pituitary adenylate-cyclase activating polypeptide (PACAP) were measured.ResultsBaseline perfusion measured in perfusion units (PU) at 32 °C was significantly lower in symptomatic RP patients (97.6 ± 22.4 PU) compared with both healthy volunteers (248.3 ± 23.5 PU, p < 0.001) and RP patients without symptoms (187.4 ± 24.9 PU, p < 0.05). After local heating to 42 °C maximum blood flow was significantly reduced in primary RP participants with current symptoms (358.6 ± 43.9 PU, p < 0.001), but not in asymptomatic ones (482.3 ± 28.7 PU, p > 0.05) when compared with healthy subjects (555.9 ± 28.2 PU). Both the area under the response curve and the latency to reach the maximum flow were significantly increased in both RP groups (symptomatic 164.6 ± 7.4 s, p < 0.001, asymptomatic 236.4 ± 17.4 s, p < 0.001) when compared with the control group (101.9 ± 4.7 s). The heat-induced percentage increase from baseline to maximal blood flow was significantly greater in symptomatic RP adolescents in comparison with healthy ones. Laboratory parameters and neuropeptide plasma levels were not altered in any groups.ConclusionTo our knowledge this is the first study in paediatric population to show altered heat-induced cutaneous hyperaemia responses in relation with the clinical severity and symptomatology.

Passive heat therapy improves cutaneous microvascular function in sedentary humans via improved nitric oxide-dependent dilation.

Passive heat therapy (repeated hot tub or sauna use) reduces cardiovascular risk, but its effects on the mechanisms underlying improvements in microvascular function have yet to be studied. We investigated the effects of heat therapy on microvascular function and whether improvements were related to changes in nitric oxide (NO) bioavailability using cutaneous microdialysis. Eighteen young, sedentary, otherwise healthy subjects participated in 8 wk of heat therapy (hot water immersion to maintain rectal temperature ≥38.5°C for 60 min/session; n = 9) or thermoneutral water immersion (sham, n = 9), and participated in experiments before and after the 8-wk intervention in which forearm cutaneous hyperemia to 39°C local heating was assessed at three microdialysis sites receiving 1) Lactated Ringer's (Control), 2) N(ω)-nitro-l-arginine (l-NNA; nonspecific NO synthase inhibitor), and 3) 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (Tempol), a superoxide dismutase mimetic. The arm used for microdialysis experiments remained out of the water at all times. Data are means ± SE cutaneous vascular conductance (CVC = laser Doppler flux/mean arterial pressure), presented as percent maximal CVC (% CVCmax). Heat therapy increased local heating plateau from 42 ± 6 to 53 ± 6% CVCmax (P < 0.001) and increased NO-dependent dilation (difference in plateau between Control and l-NNA sites) from 26 ± 6 to 38 ± 4% CVCmax (P < 0.01), while no changes were observed in the sham group. When data were pooled across all subjects at 0 wk, Tempol had no effect on the local heating response (P = 0.53 vs. Control). There were no changes at the Tempol site across interventions (P = 0.58). Passive heat therapy improves cutaneous microvascular function by improving NO-dependent dilation, which may have clinical implications.

Drug reaction with eosinophilia and systemic symptoms for phenytoin

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a hypersensitivity syndrome characterized by fever, skin eruptions, hematologic abnormalities, and systemic involvement frequently reported with anticonvulsants, allopurinol, nevirapine, and sulfasalazine. We report a case of DRESS syndrome in a patient with neurocysticercosis receiving phenytoin. A 60-year-old male patient was diagnosed with seizures due to neurocysticercosis and was prescribed phenytoin. 2 weeks after therapy, the patient had fever, burning micturition, decreased appetite, and generalized weakness for which he was treated symptomatically by a local practitioner. 2 days later, fever had recurred with generalized cutaneous hyperemia which was treated with antimicrobials in a local hospital, as it did not resolve patient was referred to our hospital. The findings on examination were icterus, periorbital edema, oral mucositis, facial puffiness, and generalized maculopapular rashes. Eosinophils, erythrocyte sedimentation rate, and liver enzymes were elevated, abdominal scan revealed hepatomegaly and cystitis. It was diagnosed as DRESS and phenytoin were discontinued. He was treated with corticosteroids. There was a clinical improvement, and liver function test was normal after a month. DRESS is a Type IV delayed hypersensitivity reaction which manifests after 2-4 weeks of treatment with an offending agent. This report indicates that the occurrence of DRESS has a higher preponderance in patients receiving phenytoin for seizures due to neurocysticercosis.

Localized hypertrichosis after index finger revascularization and complex regional pain syndrome.

Localized hypertrichosis after index finger revascularization and complex regional pain syndrome.

New approach to measure cutaneous microvascular function: an improved test of NO-mediated vasodilation by thermal hyperemia.

Cutaneous hyperemia in response to rapid skin local heating to 42°C has been used extensively to assess microvascular function. However, the response is dependent on both nitric oxide (NO) and endothelial-derived hyperpolarizing factors (EDHFs), and increases cutaneous vascular conductance (CVC) to ∼90-95% maximum in healthy subjects, preventing the study of potential means to improve cutaneous function. We sought to identify an improved protocol for isolating NO-dependent dilation. We compared nine heating protocols (combinations of three target temperatures: 36°C, 39°C, and 42°C, and three rates of heating: 0.1°C/s, 0.1°C/10 s, 0.1°C/min) in order to select two protocols to study in more depth (protocol 1; N = 6). Then, CVC was measured at four microdialysis sites receiving: 1) lactated Ringer solution (Control), 2) 50-mM tetraethylammonium (TEA) to inhibit EDHFs, 3) 20-mM nitro-L-arginine methyl ester (L-NAME) to inhibit NO synthase, and 4) TEA+L-NAME, in response to local heating either to 39°C at 0.1°C/s (protocol 2; N = 10) or 42°C at 0.1°C/min (protocol 3; N = 8). Rapid heating to 39°C increased CVC to 43.1 ± 5.2%CVCmax (Control), which was attenuated by L-NAME (11.4 ± 2.8%CVCmax; P < 0.001) such that 82.8 ± 4.2% of the plateau was attributable to NO. During gradual heating, 81.5 ± 3.3% of vasodilation was attributable to NO at 40°C, but at 42°C only 32.7 ± 7.8% of vasodilation was attributable to NO. TEA+L-NAME attenuated CVC beyond L-NAME at temperatures >40°C (43.4 ± 4.5%CVCmax at 42°C, P < 0.001 vs. L-NAME), suggesting a role of EDHFs at higher temperatures. Our findings suggest local heating to 39°C offers an improved approach for isolating NO-dependent dilation and/or assessing perturbations that may improve microvascular function.

Tempol improves cutaneous thermal hyperemia through increasing nitric oxide bioavailability in young smokers (1106.2)

We recently found that young cigarette smokers display cutaneous vascular dysfunction relative to non‐smokers, which is partially due to reduced nitric oxide (NO) synthase (NOS)‐dependent vasodilation. In this study, we tested the hypothesis that reducing oxidative stress improves NO bioavailability, enhancing cutaneous vascular function in young smokers. In ten healthy young male smokers, cutaneous vascular conductance (CVC) during local heating to 42ºC at a rate of 0.1ºC/sec was evaluated as laser‐Doppler flux divided by mean arterial blood pressure. We evaluated plateau CVC during local heating, which is known to be highly dependent on NO, at four intradermal microdialysis sites: 1) Ringer’s (control), 2) 10μM 4‐hydroxy‐2,2,6,6‐tetramethylpiperidine‐1‐oxyl (Tempol), a superoxide dismutase mimetic, 3) 10mM Nω‐Nitro‐L‐arginine (L‐NNA), a non‐specific NOS inhibitor, and 4) a combination of 10μM Tempol and 10mM L‐NNA. Tempol increased the plateau CVC compared with the Ringer’s site (90.0±2.3 vs. 77.6±3.9%max, P=0.049). Plateau CVC at the combination site (56.8±4.5%max) was lower than the Ringer’s site P=0.002), and was not different from the L‐NNA site (55.1±4.6%max) (P=0.778), indicating the Tempol effect was exclusively NO‐dependent.These data suggest that in young smokers, reducing oxidative stress improves cutaneous thermal hyperemia to local heating by enhancing NO production.Grant Funding Source: This study is supported by NIH HL081671 and The Uehara Memorial Foundation

Assessment of intravenous pbi-shRNA PDX1 nanoparticle (OFHIRNA-PDX1) in yucatan swine

PDX1 (pancreatic and duodenal homeobox 1) is overexpressed in pancreatic cancer, and its reduction results in tumor regression. Bi-functional pbi-shRNA PDX1 nanoparticle (OFHIRNA-PDX1) utilizes the endogenous micro-RNA biogenesis pathway to effect cleavage- and non-cleavage-dependent degradation of PDX1 mRNA. We have shown that OFHIRNA-PDX1 reduces pancreatic tumor volume in xenograft models. Thus, we are now exploring biorelevant large animal safety of OFHIRNA-PDX1. Mini pigs were chosen as the biorelevant species based on the similarity of human and pig PDX1 target sequence. In the initial study, animals developed fever, lethargy, hyporexia and cutaneous hyperemia following administration of OFHIRNA-PDX1. Twenty-one days later, the same animals demonstrated less toxicity with a second OFHIRNA-PDX1 infusion in conjunction with a prophylactic regimen involving dexamethasone, diphenhydramine, Indocin and ranitidine. In a new group of animals, PDX1 protein (31 kDa) expression in the pancreas was significantly repressed at 48 and 72 h (85%, P=0.018 and 88%, P=0.013; respectively) following a single infusion of OFHIRNA-PDX1 but recovered to normal state within 7 days. In conclusion, a single intravenous infusion of OFHIRNA-PDX1 in conjunction with premedication in pigs was well tolerated and demonstrated significant PDX1 knockdown.

Erectile Dysfunction Associated With Bortezomib Treatment in a Patient With Multiple Myeloma and Amyloidosis

Case Report Peripheral neuropathy (PN) is the dose-limiting toxicity of bortezomib, a reversible selective proteasome inhibitor approved for the treatment of MM. The incidence of new or worsening bortezomibinduced PN in untreated and relapsed or refractory MM is 44% and 36%, respectively, with Grade 3–4 neuropathy occurring in up to 15% of patients. Bortezomib-induced PN (BiPN) is most commonly sensory and although less frequent, motor PN has been eported, including life-threatening motor neurotoxicity. Still less ommon is autonomic neuropathy, including cutaneous hyperemia, ostural hypotension, paralytic ileus, abdominal distention, and uriary retention. We herein present the first detailed report of a patient with MM who developed erectile dysfunction (ED) after bortezomib treatment. A 60-year-old man without significant past medical history was found during a routine dental workup to have prolonged bleeding, with laboratory tests revealing iron deficiency with mild anemia and a protein gap. Work-up revealed asymptomatic IgG MM. Though a fat pad aspiration was positive for amyloidosis, biopsies taken during esophagogastroduodenoscopy and colonoscopy were Congo Red negative. Despite resolution of iron deficiency with iron

Sociodemographic characteristics, clinical signs and quality of life in patients with fibromyalgia.

We aimed to evaluate the sociodemographic and clinical characteristics as well as the quality of life of patients with fibromyalgia (FM). A total of 37 female patients diagnosed with FM and 31 healthy females were included into the study. Individuals were asked about their demographic characteristics. The number of sensitive points (NSP), skin fold sensitivity, cutaneous hyperemia and reticular skin changes of patients and healthy controls were evaluated during physical examination. Individuals were evaluated for pain severity using the Visual Analogue Scale (VAS), for psychological states using the Beck Depression Scale (BDS), for quality of life using the Short Form-36 (SF-36) and for functional status using the Fibromyalgia Impact Questionnaire (FIQ). The mean age of FM patients was 39.2±6.5 years versus 39.1±6.2 years in the controls. The most frequently encountered FM symptoms were fatigue (94.6%), sleep disturbances (86.5%) and anxiety (86.5%). Differences between FM patients and controls were statistically significant for NSP (p=0.001), VAS (p=0.001), FIQ (p=0.001), BDS (p=0.001) and SF-36 (p=0.003), and FIQ subgroups were also different between the two groups (p<0.001). In the SF-36 survey, FM patients were different from the control in the physical function (p=0.001), pain (p=0.005), general health (p=0.017), physical fitness (p=0.003), and mental health (p=0.008) portions of the survey. Fibromyalgia has distinct clinical features that lead to low functional capacity and quality of life. Thus, patients' sociodemographic characteristics and the evaluation of their quality of life may be important in the diagnosis and monitoring of treatment progress.

Inadvertent intraarterial injection of propofol in a patient under general anesthesia

injection of propofol under sedation or general anesthesia would be one of the important symptoms of intraarterial injection. In our case, the patient had an unpleasant sensation in the right metacarpophalangeal joints postoperatively. Propofol has been reported to produce vascular permeability change [3]. One case report mentioned that residual cutaneous hyperemia lasted for 12 days [4]. Furthermore, there is a possibility that intraarterial propofol attenuates capillary blood fl ow by particulate embolization or by physical interaction with blood components [5]. There may have been transient vascular hyperpermeability or a decrease in capillary blood fl ow in the present patient. Two laboratory studies [5,6] have shown that intraarterial propofol did not infl uence vasoactivity or vascular myogenic activity, and it was not toxic to the vessel wall. Intraarterial propofol has not been reported to cause irreversible sequelae, even when 8 ml of propofol was injected [1]. In contrast, the intraarterial injection of thiopental is known to cause endothelial cell destruction and necrosis, and urgent management of vasodilation or anticoagulation is required. Propofol may be a safer induction agent compared with thiopental. Nevertheless, it is important to prevent the intraarterial injection of propofol. After experiencing this incident, we have changed the color of the three-way stopcock to red, and the syringe has been connected to the three-way stopcock to avoid drug injection to the arterial route.

Deep electro-hyperthermia (EHY) with or without thermo-active agents in patients with advanced hepatic cell carcinoma: Phase II study

15168 Background: Advanced HCC has no standard chemotherapy , all pts would be valuabled in clinical trials. We evaluated effectiveness and toxicity of capacitatively coupled low-frequency 13.56 MHz deep hyperthermia (Oncotherm-EHY 2000) treatment on chemo- refractory malignant primary liver cancer which underwent all other possible treatment. Methods: From February 2005 to July 2006, we enrolled 22 pts with advanced HCC. ECOG PS was 1 or O. Viral hepatic infection status was 7 HBV+, 8 HCV+, 1 HCV/HBV+. Median age was 67,5 y (range 63 -78), male/female 20/2 . 15 pts were uneligible for liver surgery, 3 pts received TACE, 1 PEI, 1 a lot of therapy. 7 pts were pre-treated with surgery, 2 also received TACE, 1 PEI and 1 a lot of therapy. 75% of pts were in stage C of BCLC classification. 2 pts had also distant metastases, 70% of pts had portal vein thromboses. 8 pts underwent only to EHY without CT. Schedule : EHY was achieved by arrangements of capacitative electrodes with a radiofrequency field of 13.56 Mhz (RF-DHT) at 80- 130 W equivalent to 41 °- 47° C for 60 minutes, 2 times/w for 5 weeks in combination with thermo-active agents . EHY was applied over 2 time a week over 1 hour as mono - combined therapy . Concomitant chemotherapy was oxaliplatin 50 mgr at fixed dose on D 1and D 15 . One cycle is 10 treatments of EHY ; 4 pts underwent 2 cycles and 2 pts to 3 cycles and 1 pt to 4 cycles . Median number of cycles was 1,5 (range 1–4), total EHY applications were 365. Results: EHY plus thermo-active drug is beneficial on clinical conditions off treated pts with an excellent compliance on out- patients. We observed 1 CR ( pt has only one bone metastases after 6 months without liver relapse), no PR, 25% of SD. Median survival time was 20’5 weeks (5 - 81+) We noted that 11 pts (50%) presented evidence of increasing well-being. Toxicity : 4 pts had skin reaction after application of EHY. In 3 pts we observed cutaneous hyperemia on the area of treatment and mild burn on the skin ; all symptoms disappeared after local steroid therapy , treatment was interrupted until resolution . Conclusions: Low toxicity and clinical benefit will be confirmed in further clinical studies. Capacitively coupled low-frequency 13.56 deep-hyperthermia is feasible for chemo-refractory HCC. No significant financial relationships to disclose.

Perineural capsaicin treatment attenuates reactive hyperaemia in the rat skin

The neural mechanisms of reactive cutaneous hyperaemia were studied by using a novel experimental approach: the simultaneous measurement of cutaneous blood flow by laser-Doppler flowmetry in adjacent innervated and chemodenervated skin regions of the rat hindpaw served by the same artery. Transient occlusion of the femoral artery (0.5–6 min) resulted in reactive hyperaemia that was greatly reduced in the chemodenervated region. After 3 min arterial occlusion, peak cutaneous blood flow was 109±13% vs. 53±7%* (% change from baseline, n=11, * P<0.05), and the total hyperaemic response was 110±21 vs. 52±12* (arbitrary perfusion units) in intact vs. chemodenervated skin regions, respectively. The findings provide clear evidence for the involvement of peptidergic capsaicin-sensitive afferent nerves in the mechanism of reactive cutaneous hyperaemia.

Bacterial pathogens isolated from cultured bullfrogs (Rana castesbeiana).

A commercial bullfrog (Rana castesbeiana) operation in south Georgia had multiple epizootics of systemic bacterial infections over a 3-year period, 1998-2000. A number of potential pathogens (Aeromonas hydrophila, Chryseobacterium (Flavobacterium) meningosepticum, Chryseobacterium (Flavobacterium) indolgenes, Edwardsiella tarda, Citrobacterfreundii, Pseudomonas spp., and (Streptococcus iniae) were isolated from various tissues. Clinically, frogs demonstrated acute onset of torticolis, stupor, and indifference to stimuli. Cutaneous hyperemia, subcutaneous and muscular hemorrhage, and peripheral edema were consistent gross findings. Histologically, clusters of lymphocytes, monocytes, and occasional acidophiles with scattered granulomas occurred in liver, kidney, and spleen. This is the first report of S. inae and C. meningosepticum as potential disease agents in R. castesbeiana. These findings suggest that a variety of bacteria may be associated with redleg and that culture results must be obtained for accurate diagnosis.