Role of spinal cord neuropeptides in pain sensitivity and analgesia: Thyrotropin releasing hormone and vasopressin

The existence of a wide variety of neuropeptides within the spinal cord dorsal horn raises the question of their possible roles in sensory processing. The present series of behavioral experiments examined the effects of intrathecal (IT) administration of two such neuropeptides, thyrotropin-releasing hormone (TRH) and vasopressin (VAS), on pain sensitivity and antinociception. TRH exerted no marked effect on basal pain sensitivity over the dose range examined (0.25 ng-2.5 micrograms). However, a U-shaped dose-response effect on morphine antinociception (3 micrograms, IT) was observed, wherein potent attenuation, moderate attenuation, or enhancement of morphine-induced antinociception was observed following the various doses tested. In contrast, VAS produced non-opiate antinociception at the highest doses tested (25 ng and 250 ng) and none of the VAS doses (0.25 ng-250 ng) appeared to interact with IT morphine (3 micrograms) antinociception. Lastly, IT TRH was not observed to interact with IT VAS antinociception. These data provide evidence that these neuropeptides exert strikingly different effects on pain sensitivity and opiate antinociception, and provide initial evidence that TRH may be included in the growing list of neuropeptides that can act like endogenous opiate antagonists within the central nervous system.     

Panel discussion review: session two--interpretation of observed associations between multiple ambient air pollutants and health effects in epidemiologic analyses

Air pollution epidemiologic research has often utilized ambient air concentrations measured from centrally located monitors as a surrogate measure of exposure to these pollutants. Associations between these ambient concentrations and health outcomes such as lung function, hospital admissions, and mortality have been examined in short- and long-term cohort studies as well as in time-series and case-crossover studies. The issues related to interpreting the observed associations of ambient air pollutants with health outcomes were discussed at the US EPA sponsored workshop on December 13 and 14, 2006 in Chapel Hill, North Carolina, USA. The second session of this workshop focused on the following topics: (1) statistical methodology and study designs that may improve understanding of multipollutant health effects; (2) ambient concentrations as surrogate measures of pollutant mixtures; and (3) source-focused epidemiologic research. New methodology and approaches to better distinguish the effects of individual pollutants include multicity hierarchical modeling and the use of case-crossover analysis to control for copollutants. An alternative approach is to examine the mixture as a whole using principal component analysis. Another important consideration is to what extent the observed health associations are attributable to individual pollutants, which are often from common sources and are correlated, versus the pollutant mixtures that the pollutants are representing. For example, several ambient air concentrations, such as particulate matter mass, nitrogen dioxide, and carbon monoxide, may be serving as surrogate measures of motor vehicle exhaust. Source apportionment analysis is one method that may allow further advancement in understanding the source components that contribute to multipollutant health effects.     

The viscosity and viscoelasticity of blood in small diameter tubes.

Both steady and oscillatory flow of blood are studied in small rigid tubes having radii from 0.02 to 0.2 cm. This is done for rates of flow extending from higher values where nonlinear effects are evident down to very low values where the pressure to flow relations are linear. The data are analyzed using the parameters of Poiseuille theory for steady tube flow and of the linear, viscoelastic theory for oscillatory tube flow. In the low flow, linear region the apparent values of the steady flow viscosity and the oscillatory flow viscosity at 2 Hz are dependent upon the tube radius, this being in contraction with the assumptions of the theories. Another theoretical analysis is then made assuming that the blood in a boundary zone at the tube wall has modified viscous and viscoelastic properties. The measurements are in good agreement with this analysis. For low rates of flow, the steady flow is pluglike, the blood in the core moving as a solid. The pressure to flow relation is then controlled by the boundary zone for all tube radii. In this case of oscillatory flow, the core undergoes viscoelastic deformation and thus flow occurs in both the core and the boundary zone. For larger tubes, the boundary zone effects became insignificant. Under this condition the oscillatory pressure to flow relation may be used to obtain the viscoelasticity of the blood, free from the boundary layer artifacts which dominate the steady flow.     

Characterization of invasive Neisseria meningitidis from Atlantic Canada, 2009 to 2013: With special reference to the nonpolysaccharide vaccine targets (PorA,factor H binding protein,Neisseria heparin-binding antigen and Neisseria adhesin A)

BACKGROUND:Serogroup B Neisseria meningitidis (MenB) has always been a major cause of invasive meningococcal disease (IMD) in Canada. With the successful implementation of a meningitis C conjugate vaccine, the majority of IMD in Canada is now caused by MenB.OBJECTIVE:To investigate IMD case isolates in Atlantic Canada from 2009 to 2013. Data were analyzed to determine the potential coverage of the newly licensed MenB vaccine.METHODS:Serogroup, serotype and serosubtype antigens were determined from IMD case isolates. Clonal analysis was performed using multilocus sequence typing. The protein-based vaccine antigen genes were sequenced and the predicted peptides were investigated.RESULTS:The majority of the IMD isolates were MenB (82.5%, 33 of 40) and, in particular, sequence type (ST)-154 B:4:P1.4 was responsible for 47.5% (19 of 40) of all IMD case isolates in Atlantic Canada. Isolates of this clone expressed the PorA antigen P1.4 and possessed the nhba genes encoding for Neisseria heparin-binding antigen peptide 2, which together matched exactly with two of the four components of the new four-component meningococcal B vaccine. Nineteen MenB isolates had two antigenic matches, another five MenB and one meningitis Y isolate had one antigenic match. This provided 75.8% (25 of 33) potential coverage for MenB, or a 62.5% (25 of 40) overall potential coverage for IMD.CONCLUSION:From 2009 to 2013, IMD in Atlantic Canada was mainly caused by MenB and, in particular, the B:4:P1.4 ST-154 clone, which accounted for 47.5% of all IMD case isolates. The new four-component meningococcal B vaccine appeared to offer adequate coverage against MenB in Atlantic Canada.     

Genetic and antigenic analysis of invasive serogroup C Neisseria meningitidis in Canada: A decrease in the electrophoretic type (ET)-15 clonal type and an increase in the proportion of isolates belonging to the ET-37 (but not ET-15) clonal type during the period from 2002 to 2009

BACKGROUND:

Serogroup C meningococcal disease has been endemic in Canada since the early 1990s, with periods of hyperendemic disease documented in the past two decades. The present study characterized invasive serogroup C meningococci in Canada during the period from 2002 to 2009.

METHODS:

Serogroup C meningococci were serotyped using monoclonal antibodies. Their clonal types were identified by either multilocus enzyme electrophoresis or multilocus sequence typing.

RESULTS:

The number of invasive serogroup C Neisseria meningitidis isolates received at the National Microbiology Laboratory (Winnipeg, Manitoba) for characterization has dropped from a high of 173 isolates in 2001 to just 17 in 2009, possibly related to the introduction of the serogroup C meningococcal conjugate vaccine. Before 2006, 80% to 95% of all invasive serogroup C meningococci belonged to the electrophoreic type (ET)-15 clonal type, and the ET-37 (but not ET-15) type only accounted for up to 5% of all isolates. However, beginning in 2006, the percentage of the ET-15 clonal type decreased while the ET-37 (but not ET-15) type increased from 27% in 2006 to 52% in 2009. The percentage of invasive serogroup C isolates not belonging to either ET-15 or ET-37 also increased. Most ET-15 isolates expressed the antigenic formula of C:2a:P1.7,1 or C:2a:P1.5. In contrast, the ET-37 (but not ET-15) isolates mostly expressed the antigens of C:2a:P1.5,2 or C:2a:P1.2.

CONCLUSION:

A shift in the antigenic and clonal type of invasive serogroup C meningococi was noted. This finding suggests vigilance in the surveillance of meningoccocal disease is warranted.     

The impact of menopause on health-related quality of life: results from the STRIDE longitudinal study

Purpose  

We examine the impact of menopausal status, beyond menopausal symptoms, on health-related quality of life (HRQoL).     

Effects of ambient ozone on respiratory function in healthy adults exercising outdoors

The effect of exposure to ozone (O3) in ambient air on respiratory function was studied in 30 healthy adult nonsmokers engaged in a regular daily program of outdoor exercise in Tuxedo, NY during the summer of 1985. Each subject did the same exercise each day, but exercise intensity and duration varied widely between subjects, with minute ventilation ranging from 20 to 153 L and duration ranging from 15 to 55 min. Spirometry was performed immediately before and after each exercise period. O3 concentrations during exercise ranged from 21 to 124 parts per billion (ppb). All measured functional indexes showed significant (p less than 0.01) O3-associated mean decrements with FVC at -2.1 ml/ppb, FEV1 at -1.4 ml/ppb, PEFR at -9.2 ml/s/ppb, FEF25-75 at -6.0 ml/s/ppb, and FEV1/FVC at -0.038%/ppb. Mean decrements were smaller for 10 subjects with minute ventilations greater than 100 L than for 10 other subjects with minute ventilations between 60 and 100 L or for the 10 subjects with minute ventilations below 60 L. Overall, the functional decrements were similar in magnitude to those we have seen in children engaged in supervised recreational programs in summer camps. For 10 subjects with minute ventilations comparable to those used in controlled 1- and 2-h exposures to O3 in purified air in chambers (50 to 80 L), the effects were about twice as large as those reported for the chamber studies.(ABSTRACT TRUNCATED AT 250 WORDS)     

Chemical renal medullectomy. Effect on urinary prostaglandin E2 and plasma renin in response to variations in sodium intake and in relation to blood pressure

We have studied the possible vasodepressor role of the renal medulla by chemical medullectomy. Bromoethylamine hydrobromide (200 mg/kg) was injected to induce selective renal medullary necrosis in rats. The acute effects on sodium balance and long-term effects on blood pressure, plasma renin concentration (PRC) and urinary prostaglandin E2 (PGE2) were studied and compared with saline injected controls. There was an immediate and sustained increase in urine volume of low osmolality. Direct blood pressure in conscious free-moving animals was higher at 2 and 10 weeks after injection in medullary-damaged rats, although this was only significant at 10 weeks (136 +/- 3.3 vs 118 +/- 4.5 mm Hg, p less than 0.01). An initial negative sodium balance returned to normal by 7 days and rats with established medullary damage tolerated a wide range of sodium intakes. Although there was no evidence of sodium retention on the normal diet, with very high sodium loads some sodium retention was apparent since PRC was suppressed and body weight increased. Plasma creatinine and creatinine clearance were normal. PRC in rats with medullary damage was unchanged on normal diet and rose to similar levels as in control rats on low sodium intake. Urinary PGE2 was markedly reduced (148 +/- 54 vs 536 +/- 71 ng/day, p less than 0.01) in medullary damaged rats, consistent with the renal medulla being the major source of urinary PGE2. High salt intake increased urinary PGE2 in normal and proportionally in medullary damaged rats, whereas on a low sodium intake, urinary PGE2 was not different from that on the normal diet in either group.(ABSTRACT TRUNCATED AT 250 WORDS)