Antifungal activity of poly(ε-caprolactone) nanoparticles incorporated with Eucalyptus essential oils against Hemileia vastatrix.

Coffee (Coffea L.) is one of the main crops produced globally. Its contamination by the fungus Hemileia vastatrix Berkeley and Broome has been economically detrimental for producers. The objective of this work was to extract and characterize the essential oils from Eucalyptus citriodora Hook, Eucalyptus camaldulensis Dehn and Eucalyptus grandis Hill ex Maiden, produce and characterize nanoparticles containing these essential oils and evaluate the in vivo and in vitro antifungal activity of free and nanoencapsulated essential oils. The principal constituent of the essential oil from E. citriodora was citronellal; that from E. grandis was α-pinene; and that from E. camaldulensis was 1,8-cineol. The in vitro antifungal activity against the fungus H. vastatrix was 100% at a concentration of 1000 µl l-1 for all the oils and nanoparticles containing these natural products. The sizes of the nanoparticles produced with the essential oils from E. citriodora, E. camaldulensis and E. grandis were 402·13 nm, 275·33 nm and 328·5 nm, respectively, with surface charges of -11·8 mV, -9·24 mV and - 6·76 mV, respectively. Fourier transform infrared analyses proved that the encapsulation of essential oils occurred in the polymeric matrix of poly(ε-caprolactone). The incorporation of essential oils into biodegradable poly(ε-caprolactone) nanoparticles increased their efficiency as biofungicides in the fight against coffee rust, decreasing the severity of the disease by up to 90·75% after treatment with the nanoparticles containing the essential oil from E. grandis.

Receipt of Electroconvulsive Therapy and Subsequent Development of Amyotrophic Lateral Sclerosis: A Cohort Study.

We investigated the potential relationship between receipt of electroconvulsive therapy (ECT) and development of amyotrophic lateral sclerosis (ALS). We conducted a cohort study using a sample of more than one million beneficiaries enrolled in the U.S. Medicare health insurance program from 1997 to 2017. Using time-varying proportional hazard modeling, we compared ALS occurrence among patients diagnosed with psychiatric conditions who received ECT to ALS occurrence among patients diagnosed with psychiatric conditions but who did not receive ECT. We observed moderately increased, but imprecise, hazard ratios (HR) for ALS following ECT (HR = 1.39, 95% confidence interval [CI]: 0.69-2.80). A statistically significant increase in the HR of ALS was observed among those who received more than 10 ECT treatments (>10 treatments, HR = 2.24, 95% CI: 1.00-5.01), compared to those receiving no ECT, with an even stronger association observed among subjects older than 65 years (HR = 3.03, 95% CI: 1.13-8.10). No monotonic exposure-response relationship was detected in categorical analyses. Our results provide weak support for the hypothesis that receipt of ECT increases the risk of developing ALS. Additional studies in larger populations, or in populations where ECT is more common, will be needed to refute or confirm an association between receipt of ECT and subsequent development of ALS. Bioelectromagnetics. 43:81-89, 2022. © 2021 Bioelectromagnetics Society.

Vitamin D Sufficiency Has a Limited Effect on Placental Structure and Pathology: Placental Phenotypes in the VDAART Trial.

Vitamin D insufficiency during pregnancy is widespread. The effects of active vitamin D on the human placenta in vivo are unknown. We test the hypotheses that 25(OH)D sufficiency (arbitrarily defined as 25(OH)D ≥32 ng/mL) modulates placental structure and function in vivo in a population of women whose offspring are at risk for childhood asthma, and that placental pathology is more common in offspring that evolve asthma at age 3. Pregnant volunteers in the St. Louis, MO, cohort of the Vitamin D Antenatal Asthma Reduction Trial (VDAART, NIH grant #HL091528) participated in a nested case-control study and consented for the study of placentas after delivery. Maternal concentrations of 25(OH)D were measured at trial entry and in the third trimester. The histopathology of the placentas from women with sufficient 25(OH)D, versus insufficient, showed no clinically significant differences, but morphometry revealed villi of women with sufficient third-trimester 25(OH)D had a higher villous surface density. Notably, analyses of transcripts, extracted from formalin-fixed paraffin-embedded specimens, revealed higher expression of INTS9, vWF, MACC1, and ARMS2, and diminished expression of the CNTN5 genes in the insufficient group. A larger proportion of placentas showed chronic chorioamnionitis in offspring with versus without asthma at age 3. These findings suggest that maternal 25(OH)D insufficiency has a limited effect on human placental villous histopathology and morphometry, but attenuates a small number of placental gene expression profiles in this selected population. The association of placental chronic chorioamnionitis and offspring asthma is worthy of further study.

Antioxidant Consumption is Associated with Decreased Odds of Congenital Limb Deficiencies.

BACKGROUND: Approximately 1 in 2000 infants is born with a limb deficiency in the US. Research has shown that women's periconceptional diet and use of vitamin supplements can affect risk of birth defects. We investigated whether maternal consumption of nutritional antioxidants was associated with occurrence of transverse limb deficiency (TLD) and longitudinal limb deficiencies (LLD). METHODS: We analysed case-control data from mothers and their singleton infants with TLD (n = 566), LLD (n = 339), or no malformation (controls; n = 9384) in the National Birth Defects Prevention Study (1997-2009). Using a modified food frequency, we estimated usual pre-pregnancy antioxidant consumption by total fruit and vegetable consumption (in grams) grouped into tertiles, and cumulative antioxidant score (ranging from 1 to 10) based on consumption of three antioxidants: beta-carotene, lycopene, and lutein. We estimated odds ratios (OR) adjusted for maternal age, race/ethnicity, education, smoking, alcohol use, body mass index, and total energy. RESULTS: Compared to women in the lowest tertile of fruit and vegetable consumption, women in the highest tertile were less likely to have infants with TLD (OR 0.74, 95% CI 0.57, 0.96) or LLD (OR 0.82, 95% CI 0.59, 1.13). Compared to the lowest antioxidant consumption score of 1, those with the highest score of 10 had ORs of 0.68 (95% CI 0.48, 0.95) for TLD and 0.77 (95% CI 0.50, 1.17) for LLD. CONCLUSIONS: Dietary intake of antioxidants was associated with reduced odds of limb deficiencies. These findings add further evidence for women's periconceptional diet reducing occurrence of some birth defects.

Chemical characterization of the Allium sativum and Origanum vulgare essential oils and their inhibition effect on the growth of some food pathogens / Caracterização química e efeito inibitório dos óleos essenciais de Allium sativum e Origanum vulgare frente ao crescimento de alguns patógenos de alimentos

This study sought to evaluate the chemical composition of the Allium sativum and Origanum vulgare essential oils and their effect on the growth inhibition of microorganisms, such as P. aeruginosa, S. Choleraesuis, A. flavus, A. niger and P. simplicissimum, important food contaminants. The main constituents of the oregano essential oil were 4-terpineol (27.03%), γ-terpinene (20.04%), and β-cymene (6.34%), and the main constituents of the garlic essential oil were diallyl trisulfide (38, 81%), diallyl disulfide (25.23%), and methyl allyl trisulfide (12.52%). Inhibition zones were formed in in vitro tests on the bacteria S. Choleraesuis and P. aeruginosa, except for A. sativum against P. aeruginosa. The inhibition of mycelial growth caused by the oregano essential oil occurred with the concentrations of 0.10, 0.03 and 0.05 mg mL-1 for the A. flavus, A. niger and P. simplicissimum fungi, respectively. The CMI for the garlic oil began at the 0.03 mg mL-1 concentration for all species of fungi. The oils presented an inhibitory effect against the microorganisms studied and constitute an alternative for microbiological control in food.

Objetivou-se avaliar a composição química e o efeito inibitório dos óleos essenciais de Allium sativum e Origanum vulgare frente ao crescimento dos micro-organismos Pseudomonas aeruginosa, Salmonella Choleraesuis, Aspergillus flavus, Aspergillus niger e Penicillium simplicissimum, importantes patógenos causadores de contaminações em alimentos. Para quantificação e identificação dos constituintes químicos dos óleos, utilizou-se cromatógrafo gasoso acoplado a espectrômetro de massas. Os principais constituintes do óleo essencial de orégano foram o 4-terpineol (27,03%), γ-terpineno (20,04%), β-cimeno (6,34%), e do alho, o dialil trissulfeto (38,81%), dialil dissulfeto (25,23%), metil alil trissulfeto (12,52%). Os resultados dos testes in vitro sobre as bactérias S. Choleraesuis e P. aeruginosa indicaram a formação de halo de inibição e revelaram o efeito inibitório para os referidos óleos, exceto para o óleo de A. sativum frente a P. aeruginosa. Para os fungos A. flavus, A. niger e P. simplicissimum a inibição do crescimento micelial provocada pelo óleo essencial de orégano ocorreu a partir das concentrações de 0,10, 0,03 e 0,05 µg mL-1, respectivamente, sendo que a CMI para o óleo de alho iniciou-se a partir da concentração 0,03 µg mL-1 para todas as espécies de fungos. Foi possível verificar que os óleos possuem efeito inibitório sobre os microrganismos estudados, sendo, portanto, uma alternativa no controle microbiológico de alimentos.

RNA sequencing of the human milk fat layer transcriptome reveals distinct gene expression profiles at three stages of lactation.

Aware of the important benefits of human milk, most U.S. women initiate breastfeeding but difficulties with milk supply lead some to quit earlier than intended. Yet, the contribution of maternal physiology to lactation difficulties remains poorly understood. Human milk fat globules, by enveloping cell contents during their secretion into milk, are a rich source of mammary cell RNA. Here, we pair this non-invasive mRNA source with RNA-sequencing to probe the milk fat layer transcriptome during three stages of lactation: colostral, transitional, and mature milk production. The resulting transcriptomes paint an exquisite portrait of human lactation. The resulting transcriptional profiles cluster not by postpartum day, but by milk Na:K ratio, indicating that women sampled during similar postpartum time frames could be at markedly different stages of gene expression. Each stage of lactation is characterized by a dynamic range (10(5)-fold) in transcript abundances not previously observed with microarray technology. We discovered that transcripts for isoferritins and cathepsins are strikingly abundant during colostrum production, highlighting the potential importance of these proteins for neonatal health. Two transcripts, encoding ß-casein (CSN2) and α-lactalbumin (LALBA), make up 45% of the total pool of mRNA in mature lactation. Genes significantly expressed across all stages of lactation are associated with making, modifying, transporting, and packaging milk proteins. Stage-specific transcripts are associated with immune defense during the colostral stage, up-regulation of the machinery needed for milk protein synthesis during the transitional stage, and the production of lipids during mature lactation. We observed strong modulation of key genes involved in lactose synthesis and insulin signaling. In particular, protein tyrosine phosphatase, receptor type, F (PTPRF) may serve as a biomarker linking insulin resistance with insufficient milk supply. This study provides the methodology and reference data set to enable future targeted research on the physiological contributors of sub-optimal lactation in humans.

The anti-viral effect of sorafenib in hepatitis C-related hepatocellular carcinoma.

BACKGROUND: Sorafenib is currently the only approved systemic therapy shown to have efficacy in the treatment of advanced hepatocellular carcinoma (HCC). Recent studies suggest that hepatitis C (HCV)-related HCC patients derive more clinical benefit from sorafenib than other subgroups, but the mechanism for this effect is unknown. In vitro data suggest that sorafenib may exert anti-viral properties, and thus our aim in this study was to evaluate potential anti-viral activity of sorafenib in patients with HCV-related HCC. AIM: To evaluate potential anti-viral activity of sorafenib in patients with HCV-related HCC. METHODS: We prospectively enrolled patients with HCV-related HCC treated with sorafenib for up to 6 months. Baseline clinical, viral and oncologic data were collected. Patients' HCV viral loads were obtained at various time points, and compared with their baseline viral levels. No patients received any known anti-viral therapy during this time. RESULTS: Thirty-three patients were identified with baseline and subsequent HCV levels available for analysis. Six patients completed 6 months of full dose sorafenib, and comparisons of their HCV viral loads showed no significant change at week 24 (difference of means = 0.3500, CI: -0.1799-0.8799, P = 0.150), or the interim time points. Similarly, the HCV viral loads of all patients who received sorafenib and the viral loads of those patients who had tumour response to sorafenib showed no significant changes at any time point. CONCLUSION: Despite preclinical data and previous subgroup analyses suggesting that sorafenib has an anti-viral effect against HCV, this study suggests that sorafenib lacks significant anti-viral activity in HCV patients with HCC.

A randomized controlled trial comparing a multimodal intervention and standard obstetrics care for low back and pelvic pain in pregnancy.

OBJECTIVE: Women commonly experience low back pain during pregnancy. We examined whether a multimodal approach of musculoskeletal and obstetric management (MOM) was superior to standard obstetric care to reduce pain, impairment, and disability in the antepartum period. STUDY DESIGN: A prospective, randomized trial of 169 women was conducted. Baseline evaluation occurred at 24-28 weeks' gestation, with follow-up at 33 weeks' gestation. Primary outcomes were the Numerical Rating Scale (NRS) for pain and the Quebec Disability Questionnaire (QDQ). Both groups received routine obstetric care. Chiropractic specialists provided manual therapy, stabilization exercises, and patient education to MOM participants. RESULTS: The MOM group demonstrated significant mean reductions in Numerical Rating Scale scores (5.8 ± 2.2 vs 2.9 ± 2.5; P < .001) and Quebec Disability Questionnaire scores (4.9 ± 2.2 vs 3.9 ± 2.4; P < .001) from baseline to follow-up evaluation. The group that received standard obstetric care demonstrated no significant improvements. CONCLUSION: A multimodal approach to low back and pelvic pain in mid pregnancy benefits patients more than standard obstetric care.

The combination of sorafenib with transarterial chemoembolisation for hepatocellular carcinoma.

BACKGROUND: Standard of practice involves using transarterial therapy for multifocal hepatocellular carcinoma (HCC) alone and sorafenib only for more advanced HCC, but the sorafenib and transarterial therapy combination may provide greater efficacy. AIM: To evaluate the safety and efficacy of concurrent sorafenib and transarterial therapy in HCC. METHODS: Consecutive cases of HCC were treated with sorafenib and transarterial therapy, receiving sorafenib 2 to 4weeks before transarterial therapy. Baseline clinical parameters, adverse events (AEs) and survival were collected. RESULTS: A total of 47 patients received sorafenib and transarterial therapy. The majority of the patients were male (70%) with HCV (60%), median age of 60years, good performance status (0-1), stable cirrhosis (Child: A 72%; B 28%), unresectable tumour (stage: B 81%; C 19%) and median AFP of 24ng/mL. Median follow-up was 12months and median time on sorafenib was 6months. LC Bead TACE was used with a median frequency of 3. The majority of the patients (89%) experienced AEs. The most common AEs were fatigue (51%), hand-foot skin reaction (51%) and diarrhoea (43%). Grade 3 and 4 AEs included fatigue (13%) and hand-foot skin reaction (26%). Most patients required a dose reduction (66%). The main AE related to transarterial therapy was post-TACE syndrome (23%). The disease control rate was 68% at 6months. Overall median survival rate was 18.5months (95% CI 16.1-20.9months). CONCLUSION: Concurrent sorafenib and transarterial therapy is overall safe with no unexpected side effects and encouraging efficacy that warrants further study.

Óleo essencial de Baccharis tridentata Vahl: composição química, atividade antioxidante e fungitóxica, e caracterização morfológica das estruturas secretoras por microscopia eletrônica de varredura / Baccharis tridentata Vahl essential oil: chemical composition, and antioxidant and fungitoxic activities and morphological characterization of secretory structures by scanning electron microscopy

Este trabalho teve como objetivos avaliar a composição química do óleo essencial de Baccharis tridentata Vahl, as atividades antioxidante e fungitóxica, e estudar a morfologia das estruturas secretoras do óleo essencial presentes na superfície foliar por meio de microscopia eletrônica de varredura (MEV). A extração do óleo essencial foi realizada por hidrodestilação, as análises quantitativas e qualitativas foram executadas por meio de cromatografia em fase gasosa com detector de ionização de chamas (FID) e acoplada à espectrometria de massas, respectivamente. A atividade antioxidante foi realizada empregando-se os métodos de redução do radical estável DPPH e o ensaio de oxidação do sistema β-caroteno/ácido linoleico. As atividades fungitóxicas foram avaliadas utilizando o teste bioanalítico in vitro, sobre a inibição do crescimento micelial dos fitopatógenos Fusarium oxysporum, Colletotrichum gloeosporioides e Rhizoctonia solani. A composição química revelou a presença de 28 compostos, sendo o α-tujeno (22,93 por cento) o constituinte majoritário; não foi observada atividade antioxidante por meio dos ensaios utilizados, no entanto, observou-se atividade fungitóxica sobre o crescimento micelial dos fitopatógenos estudados. Já os estudos da superfície foliar por MEV revelaram a presença de tricomas glandulares em ambas as superfícies abaxial e adaxial.

This study aimed to evaluate the chemical composition and the antioxidant and fungitoxic activities of Baccharis tridentata essential oil, as well as to study the morphology of its secretory structures present on the leaf surface by scanning electron microscopy (SEM). The essential oil was extracted by hydrodistillation; the quantitative and qualitative analyses were performed on a gas chromatograph equipped with a flame ionization detector (FID) and coupled to a mass spectrometer, respectively. The antioxidant activity was determined by the methods of reduction of the DPPH stable radical and oxidation of the β-carotene/linoleic acid system. Fungitoxic activities were assessed by the in vitro bioanalytical test on the inhibition of the mycelial growth of the plant pathogens Fusarium oxysporum, Colletotrichum gloeosporioides and Rhizoctonia solani. The chemical composition revealed the presence of 28 compounds, with α-thujene (22.93 percent) as the major constituent. No antioxidant activity was observed in the tests used; however, there was fungitoxic activity against the mycelial growth of plant pathogens. Leaf surface studies by SEM revealed the presence of glandular trichomes on both abaxial and adaxial surfaces.

Review article: the management of hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma is the leading cause of death in cirrhosis. A majority of patients present at an advanced stage with poor prognosis. AIM: To review the current screening, diagnosis and management strategies involved in hepatocellular carcinoma. METHODS: A literature search was performed using PubMed for publications with a predetermined search string to identify relevant studies. RESULTS: Hepatocellular carcinoma is dramatically increasing in incidence that is mostly attributed to chronic hepatitis C and non-alcoholic fatty liver disease/non-alcoholic steatohepatitis and its clinical phenotype diabetes and obesity. Cirrhosis is the major predisposing risk factor and its presence necessitates close surveillance for hepatocellular carcinoma with serial imaging studies. Hepatocellular carcinoma can be diagnosed by its unique radiological behaviour of arterial enhancement and washout on delayed images. The Barcelona Clinic Liver Cancer staging classification system is a clinically useful algorithm for the management of patients with hepatocellular carcinoma. The simultaneous presence of cirrhosis in the patients complicates their management and monitoring for cirrhosis-related complications is important. CONCLUSIONS: Early diagnosis and definitive treatment remains the key to long-term outcome. A multidisciplinary approach is critical to the successful management of hepatocellular carcinoma. Studies combining sorafenib with locoregional or other targeted molecular therapies are likely to improve responses and outcome.

Back and pelvic pain in an underserved United States pregnant population: a preliminary descriptive survey.

OBJECTIVE: The objective of this study was to identify the prevalence of back pain and treatment satisfaction in a population of low-socioeconomic pregnant women. METHODS: This study used a cross-sectional design to determine the prevalence of self-reported musculoskeletal pain in pregnancy for 599 women. Women completed an author-generated musculoskeletal survey in the second trimester of their pregnancy that addressed pain history, duration, location, and intensity, as well as activities of daily living, treatment frequency, and satisfaction with treatment. RESULTS: Sixty-seven percent of the total population reported musculoskeletal pain, and nearly half presented with a multi-focal pattern of pain that involved 2 or more sites. Twenty-one percent reported severe pain intensity rated on a numerical rating scale. Eighty percent of women experiencing pain slept less than 4 hours per night and 75% of these women took pain medications. Importantly, 85% of the women surveyed perceived that they had not been offered treatment for their musculoskeletal disorders. CONCLUSION: Multi-focal musculoskeletal pain in pregnancy was prevalent in this underserved patient population. The pain in this population negatively affected sleep and treatment appeared inadequate.

Rapid eye movement sleep is reduced in prolactin-deficient mice.

Prolactin (PRL) is implicated in the modulation of spontaneous rapid eye movement sleep (REMS). Previous models of hypoprolactinemic animals were characterized by changes in REMS, although associated deficits made it difficult to ascribe changes in REMS to reduced PRL. In the current studies, male PRL knock-out (KO) mice were used; these mice lack functional PRL but have no known additional deficits. Spontaneous REMS was reduced in the PRL KO mice compared with wild-type or heterozygous littermates. Infusion of PRL for 11-12 d into PRL KO mice restored their REMS to that occurring in wild-type or heterozygous controls. Six hours of sleep deprivation induced a non-REMS and a REMS rebound in both PRL KO mice and heterozygous littermates, although the REMS rebound in the KOs was substantially less. Vasoactive intestinal peptide (VIP) induced REMS responses in heterozygous mice but not in KO mice. Similarly, an ether stressor failed to enhance REMS in the PRL KOs but did in heterozygous littermates. Finally, hypothalamic mRNA levels for PRL, VIP, neural nitric oxide synthase (NOS), inducible NOS, and the interferon type I receptor were similar in KO and heterozygous mice. In contrast, tyrosine hydroxylase mRNA was lower in the PRL KO mice than in heterozygous controls and was restored to control values by infusion of PRL, suggesting a functioning short-loop negative feedback regulation in PRL KO mice. Data support the notion that PRL is involved in REMS regulation.

Heat-induced changes in intracellular Na+, pH and bioenergetic status in superfused RIF-1 tumour cells determined by 23Na and 31P magnetic resonance spectroscopy.

The acute effects of hyperthermia on intracellular Na+ (Nai+), bioenergetic status and intracellular pH (pHi) were investigated in superfused Radiation Induced Fibrosarcoma-1 (RIF-1) tumour cells using shift-reagent-aided 23Na and 31P nuclear magnetic resonance (NMR) spectroscopy. Hyperthermia at 45 degrees C for 30 min produced a 50% increase in Na, a 0.42 unit decrease in pHi and a 40-45% decrease in NTP/P(i). During post-hyperthermia superfusion at 37 degrees C, pHi and NTP/P(i) recovered to the baseline value, but Na initially decreased and then increased to the hyperthermic level 60 min after heating. Hyperthermia at 42 degrees C caused only a 15-20% increase in Nai+. In the presence of 3 microM 5-(N-ethyl-N-isopropyl)amiloride (EIPA), an inhibitor of the Na+/H+ exchanger, the increase in Nai+ during 45 degrees C hyperthermia was attenuated, suggesting that the heat-induced increase in Nai+ was mainly due to an increase in Na+/H+ anti-porter activity. EIPA did not prevent hyperthermia-induced acidification. This suggests that pHi is controlled by other ion exchange mechanisms in addition to the Na+/H+ exchanger. EIPA increased the thermo-sensitivity of the RIF-1 tumour cells only slightly as measured by cell viability and clonogenic assays. The hyperthermia-induced irreversible increase in Nai+ suggests that changes in transmembrane ion gradients play an important role in cell damage induced by hyperthermia.

Nitric oxide inhibits the rate and strength of cardiac contractions in the lobster Homarus americanus by acting on the cardiac ganglion.

The lobster heart is synaptically driven by the cardiac ganglion, a spontaneously bursting neural network residing within the cardiac lumen. Here, we present evidence that nitric oxide (NO) plays an inhibitory role in lobster cardiac physiology. (1) NO decreases heartbeat frequency and amplitude. Decreased frequency is a direct consequence of a decreased ganglionic burst rate. Decreased amplitude is an indirect consequence of decreased burst frequency, attributable to the highly facilitating nature of the synapses between cardiac ganglion neurons and muscle fibers (although, during prolonged exposure to NO, amplitude recovers to the original level by a frequency-independent adaptation mechanism). NO does not alter burst duration, spikes per burst, heart muscle contractility, or amplitudes of synaptic potentials evoked by stimulating postganglionic motor nerves. Thus, NO acts on the ganglion, but not on heart muscle. (2) Two observations suggest that NO is produced within the lobster heart. First, immunoblot analysis shows that nitric oxide synthase (NOS) is strongly expressed in heart muscle relative to other muscles. Second, L-nitroarginine (L-NA), an NOS inhibitor, increases the rate of the heartbeat (opposite to the effects of NO). In contrast, the isolated ganglion is insensitive to L-NA, suggesting that heart muscle (but not the ganglion) produces endogenous NO. Basal heart rate varies from animal to animal, and L-NA has the greatest effect on the slowest hearts, presumably because these hearts are producing the most NO. Thus, because the musculature is a site of NOS expression, whereas the ganglion is the only intracardiac target of NO, we hypothesize that NO serves as an inhibitory retrograde transmitter.

Periprostatic local anesthesia eliminates pain of office-based transrectal prostate biopsy.

Up to 96% of patient who undergo prostate biopsy report pain. We performed periprostatic local anesthesia injection in an effort to improve patient acceptance of prostate biopsy. Sixty patients were randomized to receive either local injection of lidocaine in the periprostatic nerves or no anesthetic. Lidocaine was injected through a 7-inch spinal needle placed through a transrectal ultrasound biopsy guide. Ten-core biopsies were immediately performed. Following biopsy, all patients gave a Visual Analog Scale (VAS) assessment of their pain experienced during biopsy.A majority of patients reported Visual Analog Scale (VAS) scores in the moderate (28.6%) or severe (28.6%) ranges unless local anesthesia was given. Only one of 27 patients (3.7%) receiving local anesthetic reported moderate pain, and none reported severe pain. Mean VAS pain scores were 1.4 in the anesthetic group and 4.5 in the control group (P<0.0001). No difficulty was encountered from scarring in the five patients who underwent nerve spring radical retropubic prostatectomy following local anesthetic injection. Periprostatic injection of local anesthetic essentially eliminates pain from prostate biopsy. Nerve-sparing radical retropubic prostatectomy is not more difficult as a result.

Effects of hyperglycemia on oxygenation, radiosensitivity and bioenergetic status of subcutaneous RIF-1 tumors.

Since tissue oxygen tension is a balance between delivery and consumption of oxygen, considerable effort has been directed at increasing the former and/or decreasing the latter. Techniques to decrease the rate of cellular oxygen consumption (increasing the distance oxygen can diffuse into tissues) include increasing glycolysis by administering supra-physiologic levels of glucose. We have examined the effect of hyperglycemia produced by intravenous glucose infusion on the tissue oxygenation and radiation response of subcutaneously implanted murine radiation induced fibrosarcomas (RIF-1). A 0.3 M glucose solution was delivered via tail vein injection according to a protocol that maintained glucose at a plasma concentration of 17+/-1 mM. The effect of this treatment on radiation response (clonogenic and growth delay studies), tumor oxygenation (needle electrode pO2 and 2-[2-nitro-1H-imidazol-1-yl]-N-(2,2,3,3,3-pentafluoropropyl) acetamide (EF5) binding), and tumor bioenergetics and pH (31P NMR spectroscopy) was examined. Systemic measurements included hematocrit and blood glucose and lactate concentrations. The results of these studies suggest that these subcutaneously implanted RIF-1 tumors are both radiobiologically and metabolically hypoxic and that intravenous glucose infusion is not an effective method of modifying this metabolic state.