The effects of electronic nicotine vapor on voluntary alcohol consumption in female and male C57BL/6 J mice.

SIGNIFICANCE: Alcohol drinking and nicotine vaping often co-occur and dependence on both substances is common. However, the impact of nicotine vaping on alcohol consumption is not fully understood. METHODS: We examined the effects of nicotine vaping on ethanol drinking in female and male C57BL/6 J mice using an electronic nicotine delivery system and intermittent access two-bottle choice (IA-2BC) drinking. Mice were exposed to electronic nicotine vapor (3%) or propylene glycol/vegetable glycerol (PG/VG) control for 3 h sessions daily for 4 weeks and voluntary alcohol consumption was monitored. Nicotine vapor exposure was stopped and voluntary alcohol drinking was measured for a 2 week abstinence period. We also examined the effects of alcohol and nicotine on locomotion, temperature, and nicotine metabolism. RESULTS: Following acute nicotine vapor exposure, alcohol drinking was increased in males but not in females. Thermoregulation was disrupted following nicotine vapor exposure and voluntary drinking. Male and female mice displayed increased locomotor activity immediately following chronic nicotine vapor exposure, and an anxiolytic effect was seen in males. In nicotine vapor abstinence, female mice displayed increased alcohol consumption. Locomotor activity and anxiolytic effects remained elevated in male but not female mice. Female mice displayed higher levels of serum nicotine and hydroxycotinine, suggesting impaired metabolism following chronic drinking and nicotine vapor exposure. CONCLUSION: Collectively, these results suggest that while both male and female ethanol-drinking mice experience the stimulatory effects of nicotine vapor, only in males is there a parallel increase in ethanol drinking and only females display impairments in nicotine metabolism after drinking.

Electronic Nicotine Vapor Exposure Produces Differential Changes in Central Amygdala Neuronal Activity, Thermoregulation and Locomotor Behavior in Male Mice.

Nicotine is an addictive substance historically consumed through smoking and more recently through the use of electronic vapor devices. The increasing prevalence and popularity of vaping prompts the need for preclinical rodent models of nicotine vapor exposure and an improved understanding of the impact of vaping on specific brain regions, bodily functions, and behaviors. We used a rodent model of electronic nicotine vapor exposure to examine the cellular and behavioral consequences of acute and repeated vapor exposure. Adult male C57BL/6J mice were exposed to a single 3-h session (acute exposure) or five daily sessions (repeated exposure) of intermittent vapes of 120 mg/ml nicotine in propylene glycol:vegetable glycerol (PG/VG) or PG/VG control. Acute and repeated nicotine vapor exposure did not alter body weight, and both exposure paradigms produced pharmacologically significant serum nicotine and cotinine levels in the 120 mg/ml nicotine group compared with PG/VG controls. Acute exposure to electronic nicotine vapor increased central amygdala (CeA) activity in individual neuronal firing and in expression of the molecular activity marker, cFos. The changes in neuronal activity following acute exposure were not observed following repeated exposure. Acute and repeated nicotine vapor exposure decreased core body temperature, however acute exposure decreased locomotion while repeated exposure increased locomotion. Collectively, these studies provide validation of a mouse model of nicotine vapor exposure and important evidence for how exposure to electronic nicotine vapor produces differential effects on CeA neuronal activity and on specific body functions and behaviors like thermoregulation and locomotion.

Thermogenic capacity at subzero temperatures: how low can a hibernator go?

Abstract Hibernation in mammals is a physiological and behavioral adaptation to survive intervals of low resource availability through profound decreases in metabolic rate (MR), core body temperature (Tb), and activity. Most small mammalian hibernators thermoconform, with Tb approximating ambient temperature (Ta); arctic species are an exception, since they must actively defend what can be large thermal gradients between Tb and Ta. Here we compare the thermogenic capacity of the arctic ground squirrel (Urocitellus parryii) to that of the golden-mantled ground squirrel (Callospermophilus lateralis), a temperate-zone montane hibernator. We allowed animals to reenter torpor at sequentially lower Ta's and found that arctic ground squirrels maintained steady state torpor at Ta's as low as -26°C, through a 36-fold increase in torpid MR (TMR), compared to their minimum TMR, exhibited at a Ta of 0°C. Golden-mantled ground squirrels are able to maintain steady state torpor at Ta's at least as low as -8°C, through a 13.5-fold increase in MR, compared to their minimum TMR at a Ta of 2°C. In a second experiment, torpid animals were exposed to continuously decreasing Ta's (0.25°C/30 min); individuals of both species increased their metabolism while remaining torpid at low Ta's (as low as -30°C for arctic ground squirrels and -10°C for golden-mantled ground squirrels). Although the capacity to hibernate at subfreezing Ta's is not unique to arctic ground squirrels, their large body size, greater torpid metabolic scope, and previously ascribed capacity to supercool allow them to occupy much colder hibernacula for prolonged seasons of hibernation.

Red tides in the Gulf of Mexico: Where, when, and why?

[1] Independent data from the Gulf of Mexico are used to develop and test the hypothesis that the same sequence of physical and ecological events each year allows the toxic dinoflagellate Karenia brevis to become dominant. A phosphorus-rich nutrient supply initiates phytoplankton succession, once deposition events of Saharan iron-rich dust allow Trichodesmium blooms to utilize ubiquitous dissolved nitrogen gas within otherwise nitrogen-poor sea water. They and the co-occurring K. brevis are positioned within the bottom Ekman layers, as a consequence of their similar diel vertical migration patterns on the middle shelf. Upon onshore upwelling of these near-bottom seed populations to CDOM-rich surface waters of coastal regions, light-inhibition of the small red tide of ~1 ug chl l(-1) of ichthytoxic K. brevis is alleviated. Thence, dead fish serve as a supplementary nutrient source, yielding large, self-shaded red tides of ~10 ug chl l(-1). The source of phosphorus is mainly of fossil origin off west Florida, where past nutrient additions from the eutrophied Lake Okeechobee had minimal impact. In contrast, the P-sources are of mainly anthropogenic origin off Texas, since both the nutrient loadings of Mississippi River and the spatial extent of the downstream red tides have increased over the last 100 years. During the past century and particularly within the last decade, previously cryptic Karenia spp. have caused toxic red tides in similar coastal habitats of other western boundary currents off Japan, China, New Zealand, Australia, and South Africa, downstream of the Gobi, Simpson, Great Western, and Kalahari Deserts, in a global response to both desertification and eutrophication.

Do antepartum herpes simplex virus cultures predict intrapartum shedding for pregnant women with recurrent disease?

OBJECTIVE: To examine antenatal screening as a predictor of intrapartum shedding of herpes simplex virus (HSV) and to determine its usefulness in guiding the appropriate route of delivery for patients with recurrent HSV in pregnancy. METHODS: A population of 198 pregnant women with a history of recurrent genital HSV were cultured in the last weeks of their pregnancy by specially-trained personnel and intrapartum by their delivering attendants. RESULTS: Of cultures from a total of 906 antenatal visits, 17% were culture positive, with an asymptomatic shedding rate of 3.4%. Asymptomatic shedding occurred in 12.6% of women. Over the 8-week antepartum period, viral culture-positivity rates for each visit ranged from 11% to 19.5%. This provided an expected delivery culture-positivity rate of 15.3%. However, actual intrapartum viral culture positivity occurred in only three of 191 women (1.5%; P < 0.001). Because previous studies have suggested antepartum culture positivity fails to predict intrapartum viral shedding, evaluations, including cultures, as well as predictive values for subsequent culture positivities, were determined under the supervision of an infectious disease specialist. Under these conditions, positive predictive values were 59% when the interval between visits was 2 days, but only 19% when days between visits were >2 (P < 0.0001). No cases of neonatal herpes were seen in this population, although cesarean deliveries were performed in 31% of the patient population, with genital herpes as the indication for 56% of those. CONCLUSIONS: Antepartum serial screening by viral culture is not predictive of an infant's risk of intrapartum viral exposure when conducted at weekly intervals. However, more frequent assessments of patients can be predictive of an infant's exposure risk to HSV; for patients with frequent recurrent disease near term or primary infection in pregnancy, frequent late antepartum screening may be appropriate.

Chirped femtosecond pulse scattering by spherical particles.

Generalized Lorentz-Mie formulas are used to study the scattering characteristics when a chirped femtosecond pulse illuminates a spherical particle. For a linear chirped Gaussian pulse with the envelope function g(τ) = exp[-π(1 + ib)τ(2)], dimensionless parameter b is defined as a chirp. The calculation illustrated that even for pulses with a constant carrier wavelength (λ(0) = 0.5 µm) and pulse-filling coefficient (l(0) = 1.98), the efficiencies for extinction and scattering differ very much between the carrier wave and the different chirped pulses. The slowly varying background of the extinction and the scattering curves is damped by the chirp. When the pulse is deeply chirped, the maxima and minima of the background curves reduce to the point where they disappear, and the efficiency curves illustrate a steplike dependence on the sphere size. Another feature is that the chirped-pulse scattering seems blind: it depends only on the amount of chirp (|b|), regardless of upchirp (b > 0) or downchirp (b< 0).

Automated microneutralization: method and comparison with western blot for type-specific detection of herpes simplex antibodies in two pregnant populations.

A novel method for the detection of microneutralization was compared to Western blot for detection of type-specific antibodies to herpes simplex virus in two pregnant patient populations in Vancouver. From an unselected group of women in labor in a tertiary care obstetric hospital (426) and another group of women specially referred for assessment of genital herpes in pregnancy (195) 20 and 88%, respectively, were seropositive for herpes simplex virus type 2 antibodies by Western blot. During the study period, 93 (48%) of the high-risk group were culture positive for HSV-2 and all but one case was verified serologically by Western blot. Therefore, the sensitivity for Western blot in this high seroprevalence group was 99%. The false-negative case had longstanding recurrent infection and on retest was found to be a laboratory error. For microneutralization, type-specificity was especially difficult to distinguish among patients with mixed viral type patterns. Comparing microneutralization to Western blot as the gold standard, sensitivity, specificity, positive and negative predictive values were 84, 78, 97 and 40% respectively, for the referred group and 73, 82, 51 and 92%, respectively, for the unselected group. Poor negative and positive predictive values for the referred group and unselected populations, respectively, demonstrate that microneutralizations are not clinically acceptable for type-specific antibody detection. By contrast, serology by Western blot is very sensitive and apparently highly specific.

Thalamic neuron theory: theoretical basis for the role played by the central nervous system (CNS) in the causes and cures of all diseases.

The Thalamic Neuron Theory (TNT) postulates that the central nervous system (CNS) is involved in all disease processes, as the CNS not only processes incoming physical and chemical information from the periphery, it also sends out physiological commands to the periphery in order to maintain homeostasis for the entire body. Inherent in its capacity to learn and adapt (i.e. to habituate) is the CNS' ability to learn to be sick (pathological habituation) by looking in certain deranged central neural circuitries, leading to chronic disease states. These pathologically habituated states can be reversed by dehabituation through manipulation or modulation of the abnormal neural circuits by physical means (physical neuromodulation) like acupuncture, or chemical means (chemoneuromodulation) such as Chinese medicine, homeopathy or other modern medical techniques in a repetitious manner to mimic the habituation process. Chemoneuromodulation can also be achieved by delivery of minute amounts of pharmacological agents to specific sites in the periphery such as the acupuncture loci. It is hypothesized that humoral and neurotrophic factors and cytokines could be highly effective neuromodulating agents. TNT assumes the blue print for embryological development is embodied in the phylogenetically ancient part of the brain. This primordial master plan, organized in the form of a homunculus, possibly encased in a small nucleus, retains control over the subsequently evolved parts of the brain so that the entire CNS functions like a composite homunculus which controls the physiological functions of the entire body. TNT further postulates that the master homunculus takes the shape of a curled up embryo with its large head buried close to its pelvic region, with its large feet and hands crossed over to the contralateral sides. Neuronal clusters along a neuronal chain in the homunculus represent acupuncture points in the periphery. The neuronal chain itself represents a meridian and Chi is nothing more than the phenomenon of neurotransmissions. Certain new theoretical concepts such as the principles of Adynamic Stat and Bilaterality are also presented. Many difficult to explain clinical observations in modern medicine, Chinese herbal medicine, acupuncture and homeopathy can now be adequately explained using TNT. Based on this model, new therapeutic techniques can be launched to combat a whole host of intractable diseases.

Analysis of LINE-1 family sequences on a single monkey chromosome.

The structure of LINE-1 (L1Ca) family members present on African green monkey chromosome CAE-19 is compared with that of the entire set of L1Ca sequences present in the monkey genome. The analysis involved annealing of cloned subsegments of monkey L1 family members to DNA-blots containing restriction endonuclease digests of either total monkey liver DNA or DNA isolated from a monkey/mouse somatic cell hybrid carrying the single monkey chromosome. In addition, L1Ca segments cloned from hybrid cell DNA were characterized by restriction endonuclease mapping and hybridization. The data indicate that, taken as a whole, the set of L1Ca sequences on CAE-19 tends to differ in characteristic ways from the set present in the total monkey genome.

Florida current: low-frequency variability as observed with moored current meters during april 1982 to june 1983.

A 1-year time series of volume transport through the Florida Straits near 27 degrees N was derived from an array of five subsurface current meter moorings. The transport estimates, determined on the basis of constant shear extrapolation of the subsurface velocities to the surface, are in good agreement with transports derived from submarine cable and Pegasus measurements. The annual transport cycle in 1982-1983 is complicated by large-amplitude fluctuations on time scales of 1 to 3 weeks, but it does exhibit a transport maximum in summer and a minimum in fall-winter, consistent with historical results and of similar magnitude. The energy density spectrum of transports is continuous with a slope of about -1.5 and does not show a gap between the periods of weeks and seasonal. Evidence was found for atmospheric forcing of transport fluctuations, with highest coherence between transport and the local meridional wind stress at periods of 10 and 15 days during the summer and 5 and 40 days during the winter.

Continuous reorganization leads to extensive polymorphism in a monkey centromeric satellite.

Previously we reported the existence of a highly polymorphic satellite, deca-satellite, in the African green monkey genome; deca-satellite probe anneals to complex sets of repeated restriction endonuclease fragments that differ from individual to individual in the monkey population. Here we present experiments aimed at clarifying the structure and organization of deca-satellite sequences and investigating the mechanisms that generate the polymorphisms. Deca-satellite represents less than 1% of the monkey genome but the percentage varies from one monkey to another. The core sequence 5'-C-C-G-G within the ten base-pair deca-satellite repeat unit is well conserved and the central 5'-C-G is sometimes but not always methylated. Restriction endonuclease analysis with BamHI and EcoRI defines separate satellite domains that have evolved in an independent manner. In situ hybridization shows deca-satellite to be located at the centromeric regions of some but not all monkey chromosomes. This location is independently confirmed by a high frequency, in monkey libraries, of segments containing junctions between deca-satellite and alpha-satellite, the main monkey centromeric satellite. The total number of metaphase chromosomes that show centromeric grains after in situ hybridization with a deca-satellite probe varies from one monkey to another. Moreover, in situ hybridization to endoreduplicated diplochromosomes showed that deca-satellite is occasionally distributed asymmetrically on one or the other of the two pairs of sister chromatids in one diplochromosome. This indicates that major reorganization of the satellite can occur frequently in somatic cells. We discuss several possible mechanisms by which deca-satellite sequences could be either amplified or deleted during a single replicative cycle. Also, on the basis of the marked fluidity of deca-satellite abundance and organization and other well-known attributes of centromeric satellites, we suggest that the existence and maintenance of centromeric satellite rests on the role of the tandem repeats themselves and not on any particular nucleotide sequence, repeat length or organization.

Recurring defective variants of simian virus 40 containing monkey DNA segments.

Four independently and newly isolated defective variants of simian virus 40 have been characterized. All four are very similar, if not identical, to two previously and independently isolated variants (Wakamiya et al., J. Biol. Chem. 254:3584-3591, 1979; J. Papamatheakis, E. Kuff, E. Winocour, and M. F. Singer, J. Biol. Chem. 255:8919-8927, 1980). The documented similarities include restriction endonuclease maps and the presence of the same monkey DNA segments covalently linked to simian virus 40 DNA sequences. Each of the newly described variants was first detected upon serial passaging of wild-type simian virus 40 at a high multiplicity of infection at 33 degrees C as recently described (M. F. Singer and R. E. Thayer, J. Virol. 35:141-149, 1980). A variety of experiments support the idea that the various isolates were independent and do not reflect inadvertent cross-contamination. Two of the new isolates arose during passage of wild-type strain 777 virus in BSC-1 cells, one during passage of strain 776 in BSC-1 cells, and one during passage of strain 776 in primary African green monkey kidney cells. The two variants obtained after passage of strain 776 were shown to contain a particular recognition site for restriction endonuclease MboII within their simian virus 40 DNA segments, as do the two previous isolates. This site is not present in wild-type strain 776 DNA but is shown here to be present in wild-type strain 777 DNA. The surprising recurrence of closely related variants and particularly the unexpected presence of the endo R.MboII site in variants derived from passaging strain 776 suggest that these variants may arise by mechanisms other than recombination between the initial infecting viral genome and the host DNA.

Thalamic neuron theory: a hypothesis concerning pain and acupuncture.

A new theory is proposed to explain various pain phenomena hitherto unexplainable. It is hypothesized that neurons in the thalamic region are responsible for the generation of most pain, particularly in chronic pain states. It is also hypothesized that the thalamic neurons are organized according to a master scheme representing a homunculus in the fetal position. Various painful conditions and the treatments of them including the trigger points phenomena, neurosurgical techniques, acupuncture and acupuncture anesthesia can be explained on this basis.

Lidocaine injection of auricular points in the treatment of insomnia.

By combining knowledge in modern medicine and traditional Chinese medicine, auricular points were selected for treatment of insomnia. Instead of the placement of needles, injection of small amounts of Lidocaine into these sites was employed. Fifteen out of 16 patients obtained substantial improvement and one patient received moderate improvement. The therapeutic effect was maintained three months after the end of the treatment series. The physiological and clinical implications of this study in terms of modern medicine and traditional Chinese medicine are also discussed.