Application of a hybrid computational fluid dynamics and physiologically based inhalation model for interspecies dosimetry extrapolation of acidic vapors in the upper airways

This study provides a scientific basis for interspecies extrapolation of nasal olfactory irritants from rodents to humans. By using a series of short-term in vivo studies, in vitro studies with nasal explants, and computer modeling, regional nasal tissue dose estimates were made and comparisons of tissue doses between species were conducted. To make these comparisons, this study assumes that human and rodent olfactory epithelium have similar susceptibility to the cytotoxic effects of organic acids based on similar histological structure and common mode of action considerations. Interspecies differences in susceptibility to the toxic effects of acidic vapors are therefore assumed to be driven primarily by differences in nasal tissue concentrations that result from regional differences in nasal air flow patterns relative to the species-specific distribution of olfactory epithelium in the nasal cavity. The acute, subchronic, and in vitro studies have demonstrated that the nasal olfactory epithelium is the most sensitive tissue to the effects of inhalation exposure to organic acids and that the sustentacular cells are the most sensitive cell type of this epithelium. A hybrid computational fluid dynamics (CFD) and physiologically based pharmacokinetic (PBPK) dosimetry model was constructed to estimate the regional tissue dose of organic acids in the rodent and human nasal cavity. The CFD-PBPK model simulations indicate that the olfactory epithelium of the human nasal cavity is exposed to two- to threefold lower tissue concentrations of a representative inhaled organic acid vapor, acrylic acid, than the olfactory epithelium of the rodent nasal cavity when the exposure conditions are the same. The magnitude of this difference varies somewhat with the specific exposure scenario that is simulated. The increased olfactory tissue dose in rats relative to humans may be attributed to the large rodent olfactory surface area (greater than 50% of the nasal cavity) and its highly susceptible location (particularly, a projection of olfactory epithelium extending anteriorly in the dorsal meatus region). In contrast, human olfactory epithelium occupies a much smaller surface area (less than 5% of the nasal cavity), and it is in a much less accessible dorsal posterior location. In addition, CFD simulations indicate that human olfactory epithelium is poorly ventilated relative to rodent olfactory epithelium. These studies suggest that the human olfactory epithelium is protected from irritating acidic vapors significantly better than rat olfactory epithelium due to substantive differences in nasal anatomy and nasal air flow. Furthermore, the general structure of the hybrid CFD-PBPK model used for this study appears to be useful for target tissue dosimetry and interspecies dose comparisons for a wide range of inhaled vapors.     

Reexamination of tympanic membrane temperature as a core temperature

Controversies surrounding tympanic temperature (Tty) itself and techniques for measuring it have dampened the potential usefulness of Tty in determining core temperature (operationally defined here as the body temperature taken at a deep body site). The present study was designed to address the following questions. 1) Can a tympanic membrane probe be made that is safer and more reliable than its predecessors? 2) Why is the effect of facial cooling and heating on Tty so inconsistent in reports from different laboratories? 3) Is Tty still useful as a measure of core temperature? Data from this study, obtained with a modified thermocouple probe, suggest that the widely reported facial skin cooling effect on Tty is most probably due to thermal contamination from the surrounding ear canal wall and/or suboptimal contact of the probe sensor with the tympanic membrane because 1) Tty that fell during facial cooling was increased to the precooling level by the repositioning of the probe sensor; 2) Tty determined by using a probe with a larger sensor area (the sensor soldered to a steel wire ring)tended to fall in response to facial cooling, whereas Tty determined with a thermally insulated probe ring did not; and 3) Tty obtained under careful positioning of the insulated probe was relatively insensitive to facial cooling or heating. Because Tty was practically identical to esophageal temperature (Tes) in the steady state, i.e., 36.83 +/- 0.20 (SD) degrees C for Tty and 36.87 +/- 0.16 degrees C for Tes at room temperature (n = 11), and because facial cooling had little effect on both Tty and Tes (36.86 +/- 0.17 degrees C for Tty and 36.86 +/- 0.26 degrees C for Tes during facial or scalp skin cooling), we support the postulate that Tty is a good measure of core temperature. The temperature transient in response to foot warming was detected 5 min (n = 2) faster with Tty than with Tes. Thus, with further improvements in the design of the probe. Tty can become a standard for determination of core body temperature.     

Screening for PTSD in a substance abuse sample: psychometric properties of a modified version of the PTSD Symptom Scale Self-Report. Posttraumatic stress disorder

The high rate of posttraumatic stress disorder (PTSD) among substance use disorder (SUD) patients has been documented in research protocols, but there is evidence that it is markedly under-diagnosed in clinical settings. To address the need for a brief self-report measure to identify SUD patients who may benefit from further assessment and/or treatment for PTSD, the psychometric properties of a modified version of the PTSD Symptom Scale Self-Report (PSS-SR) were examined in a treatment-seeking SUD sample (N = 118). The modified version of the PSS-SR, which measures both frequency and severity of PTSD symptoms, demonstrated good internal consistency reliability and was correlated with other self-report measures of trauma-related symptomatology. Comparisons between a structured PTSD diagnostic interview and the modified PSS-SR indicated that 89% of the PTSD positive patients were correctly classified by the modified PSS-SR. The clinical relevance of these findings was discussed.     

Closed rupture of the anterior tibial tendon. A case report

Closed subcutaneous rupture of the anterior tibial tendon is a relatively uncommon injury that requires a thorough clinical examination to diagnose correctly. The authors report a case of this disorder and provide a review of the relevant literature. A method of surgical repair not previously described in the literature is also presented.     

Involvement of calcium in interactions between gingival epithelial cells and Porphyromonas gingivalis

Porphyromonas gingivalis, a periodontal pathogen can invade primary cultures of gingival epithelial cells. This invasion was significantly inhibited (74-81%) by thapsigargin and 1,2-bis(2-aminophenoxy)ethane-N,N,N1,N1-tetraacetic acid, acetoxymethyl ester (BAPTA/AM), but not by EDTA or amiloride. Release of Ca2+ from an intracellular store and the subsequent increase in cytosolic [Ca2+] may, therefore, be involved in the invasion process, while Ca2+ influx is not. Moreover, cytosolic [Ca2+] was found to increase transiently in about 30% of gingival epithelial cells acutely exposed to P. gingivalis, but not in unexposed cells, or in cells exposed to noninvasive Escherichia coli. These findings indicate that P. gingivalis invasion of epithelial cells is correlated with activation of [Ca2+]-dependent host cell signaling systems.