A network pharmacology and molecular docking approach in the exploratory investigation of the biological mechanisms of lagundi (Vitex negundo L.) compounds against COVID-19.

Coronavirus disease 2019 (COVID-19) is an inflammatory and infectious disease caused by severe acute respiratory syndrome coronavirus 2 virus with a complex pathophysiology. While COVID-19 vaccines and boosters are available, treatment of the disease is primarily supportive and symptomatic. Several research have suggested the potential of herbal medicines as an adjunctive treatment for the disease. A popular herbal medicine approved in the Philippines for the treatment of acute respiratory disease is Vitex negundo L. In fact, the Department of Science and Technology of the Philippines has funded a clinical trial to establish its potential as an adjunctive treatment for COVID-19. Here, we utilized network pharmacology and molecular docking in determining pivotal targets of Vitex negundo compounds against COVID-19. The results showed that significant targets of Vitex negundo compounds in COVID-19 are CSB, SERPINE1, and PLG which code for cathepsin B, plasminogen activator inhibitor-1, and plasminogen, respectively. Molecular docking revealed that α-terpinyl acetate and geranyl acetate have good binding affinity in cathepsin B; 6,7,4-trimethoxyflavanone, 5,6,7,8,3',4',5'-heptamethoxyflavone, artemetin, demethylnobiletin, gardenin A, geranyl acetate in plasminogen; and 7,8,4-trimethoxyflavanone in plasminogen activator inhibitor-1. While the results are promising, these are bound to the limitations of computational methods and further experimentation are needed to completely establish the molecular mechanisms of Vitex negundo against COVID-19.

A network pharmacology and molecular docking approach in the exploratory investigation of the biological mechanisms of lagundi (Vitex negundo L.) compounds against COVID-19

Coronavirus disease 2019 (COVID-19) is an inflammatory and infectious disease caused by severe acute respiratory syndrome coronavirus 2 virus with a complex pathophysiology. While COVID-19 vaccines and boosters are available, treatment of the disease is primarily supportive and symptomatic. Several research have suggested the potential of herbal medicines as an adjunctive treatment for the disease. A popular herbal medicine approved in the Philippines for the treatment of acute respiratory disease is Vitex negundo L. In fact, the Department of Science and Technology of the Philippines has funded a clinical trial to establish its potential as an adjunctive treatment for COVID-19. Here, we utilized network pharmacology and molecular docking in determining pivotal targets of Vitex negundo compounds against COVID-19. The results showed that significant targets of Vitex negundo compounds in COVID-19 are CSB, SERPINE1, and PLG which code for cathepsin B, plasminogen activator inhibitor-1, and plasminogen, respectively. Molecular docking revealed that α-terpinyl acetate and geranyl acetate have good binding affinity in cathepsin B; 6,7,4-trimethoxyflavanone, 5,6,7,8,3',4',5'-heptamethoxyflavone, artemetin, demethylnobiletin, gardenin A, geranyl acetate in plasminogen; and 7,8,4-trimethoxyflavanone in plasminogen activator inhibitor-1. While the results are promising, these are bound to the limitations of computational methods and further experimentation are needed to completely establish the molecular mechanisms of Vitex negundo against COVID-19.

Overexpression of protein S100A4 is independently associated with overall survival in stage C colonic cancer but only in cytoplasm at the advancing tumour front.

PURPOSE: S100A4, a multifunctional protein, has been linked to the invasive growth and metastases of several human cancers. This study investigated the association between S100A4 and overall survival and other clinicopathological features in patients with stage C colonic cancer. METHODS: Clinical and pathological data were obtained from a prospective hospital registry of 409 patients who had a resection for stage C colonic cancer. Tissue microarrays for immunohistochemistry were constructed from archived tissue. S100A4 staining intensity and percentage of stained cells were assessed in nuclei and cytoplasm for both the central part of the tumour and at the advancing front. Overall survival was analysed by the Kaplan-Meier method and Cox regression. RESULTS: Only a high percentage of cells with S100A4 cytoplasmic staining in frontal tissue was associated with poor survival (hazard ratio, 1.6; 95 % CI 1.1-2.2; p = 0.008) after adjustment for other prognostic variables. There was no association between frontal cytoplasmic S100A4 expression and any of 13 other clinicopathological variables. CONCLUSIONS: High expression of S100A4 in cytoplasm at the advancing front of stage C colonic tumours indicates a poor prognosis. Whether S100A4 can predict response to adjuvant chemotherapy remains to be investigated in a randomised clinical trial.

hERG subunit composition determines differential drug sensitivity.

BACKGROUND AND PURPOSE: The majority of human ether-a-go-go-related gene (hERG) screens aiming to minimize the risk of drug-induced long QT syndrome have been conducted using heterologous systems expressing the hERG 1a subunit, although both hERG 1a and 1b subunits contribute to the K+ channels producing the repolarizing current I(Kr) . We tested a range of compounds selected for their diversity to determine whether hERG 1a and 1a/1b channels exhibit different sensitivities that may influence safety margins or contribute to a stratified risk analysis. EXPERIMENTAL APPROACH: We used the IonWorks™ plate-based electrophysiology device to compare sensitivity of hERG 1a and 1a/1b channels stably expressed in HEK293 cells to 50 compounds previously shown to target hERG channels. Potency was determined as IC50 values (µM) obtained from non-cumulative, eight-point concentration-effect curves of normalized data, fitted to the Hill equation. To minimize possible sources of variability, compound potency was assessed using test plates arranged in alternating columns of cells expressing hERG 1a and 1a/1b. KEY RESULTS: Although the potency of most compounds was similar for the two targets, some surprising differences were observed. Fluoxetine (Prozac) was more potent at blocking hERG 1a/1b than 1a channels, yielding a corresponding reduction in the safety margin. In contrast, E-4031 was a more potent blocker of hERG 1a compared with 1a/1b channels, as previously reported, as was dofetilide, another high-affinity blocker. CONCLUSIONS AND IMPLICATIONS: The current assays may underestimate the risk of some drugs to cause torsades de pointes arrhythmia, and overestimate the risk of others.

Influence of petroleum hydrocarbons on the endoparasitic helminths of the common eider, Somateria mollissima, from Newfoundland.

A comparison of commonly occurring metazoan parasites in the digestive tract was made between common eiders, Somateria mollissima, that were contaminated with oil and reference birds confiscated from illegal hunting. There was a greater number of commonly occurring parasites and their abundance in reference than in oiled eiders. Except for an acanthocephalan, Polymorphus botulus, which was embedded in the wall of the intestinal tract, most of the other taxa of parasites, including trematodes, cestodes and nematodes, were probably voided from the birds following ingestion of oil. Reference eiders harboured fewer species and a substantially lower mean abundance of parasites than those studied in Newfoundland and Labrador more than four decades ago; this may be a signal of a changing prey base or an increase in prey availability as winter ice cover continues to decline.

Effects of dietary protein concentration and specific amino acids on body weight, body composition and feather growth in young turkeys.

1. Two randomised block factorial experiments were conducted to investigate the relationships between the effects of dietary crude protein and specific amino acid concentrations on the relative growth of the body and feathers of young turkeys. 2. Decreasing dietary crude protein concentration from 300 to 180 g/kg in experiment 1 reduced the body and breast muscle weights of a large male line of turkeys proportionally by 0.44 and 0.52 compared with 0.19 and 0.24 in a small traditional line. 3. Decreasing dietary crude protein concentration was associated with a maximum reduction in feather weight of 0.18 and 0.24 respectively in male line and traditional turkeys. The length of the feathers in the cranial region of the breast decreased from 26 to 19mm in the traditional line compared with an increase from 14 to 25 mm in male line turkeys. 4. Decreasing dietary crude protein concentration was associated with an increase in the fat content of the feather-free carcase. Male line turkeys had a higher carcase fat and lower feather dry matter content than the traditional turkeys. 5. It was concluded that dietary crude protein was preferentially partitioned to feather rather than muscle growth in the male line in contrast to a traditional line of turkeys in which the growth of feathers and muscle were affected equally. 6. In experiment 2, the amino acids arginine, valine, methionine and tyrosine were added separately to a common basal ration (180g CP/kg) to raise their concentration to that of the control ration (260 g CP/kg). Each ration was fed ad libitum to male line turkeys from 2 to 6 weeks of age. 7. Amino acid supplementation increased body and breast muscle weights. 8. Compared with the basal ration, tyrosine was associated with a reduction in feather weight whereas valine had no effect. Supplementation with arginine and methionine resulted in increased feather weights that were similar to that of the controls. 9. It was concluded that arginine and methionine were used preferentially and are essential for feather growth. Excess amino acids that are not required for feather growth such as tyrosine and valine were used for increased body growth and resulted in relatively poor feather cover. 10. The results suggest that feather growth was maintained as much as possible at the expense of body growth when the amino acid concentration of the ration was less than that required to maximise body and muscle weight gain in large male line turkeys.

Management of late complications of pelvic radiation in the rectum and anus: a review.

PURPOSE: Radiotherapy has become one of the most important treatment modalities for human malignancy. Tumors affecting the organs of the pelvis are increasingly being irradiated for local treatment benefit, with the subsequent complication of anorectal injury of varying extent. The aim of this review is to determine how to manage the consequences of long-term effects of radiotherapy on the rectum and anus. METHODS: A comprehensive search of the literature with manual cross-referencing was performed using the MEDLINE, PubMed, and Cochrane Databases. RESULTS: Long-term manifestations of injury caused by pelvic radiotherapy include abscess and fistula formation, stricture, mucus discharge, urgency, tenesmus, diarrhea, increased risk of cancer, and most commonly, bleeding. Most patients present with several symptoms; however, usually one symptom dominates. CONCLUSIONS: Many of these symptoms are self-limiting, and mucosal complications may often be treated by nonsurgical methods such as topical formalin application, endoscopic argon plasma coagulation, and hyperbaric oxygen therapy. Conservative measures have not been shown to be of benefit if symptoms persist. Structural abnormalities and septic complications are likely to require surgery. Modern techniques in the delivery of radiotherapy help minimize the likelihood of rectal complications.

Early clinical exposure to people who are dying: learning to care at the end of life.

BACKGROUND: The nature of medical care at the end of life and, in particular, the way in which caring is learned remain problematic for medical educators and the profession. Recent work has indicated that doctors learn to care, in an emotional and intimate way, from people who are dying. METHODS: This paper reports on the development of a programme designed for medical students in their first clinical year who spend time with a person who is dying and their family. The students are required to produce a portfolio assignment that includes a personal reflection of the experience. The findings from a phenomenological study undertaken using these personal reflections are reported. These reflections and comments are interpreted as being embedded in five key themes. RESULTS: The actual encounters differed from the medical students' anticipation of them. Students identified an emotional component to the experience; they explored their own and the patient's understandings of spirituality; they reflected on personal meanings of the encounter and they suggested ways in which they might learn to care more effectively for people who are dying. DISCUSSION: The way in which many of these students approach end-of-life care has been altered through a transformative educational experience that encouraged them to draw on their own experiences and skills. Their learning was facilitated by the writing of accounts and the discussion that each group held with teaching staff at the conclusion of the programme.

Effects of dietary calcium and phosphorus on mineral retention, growth, feed efficiency and walking ability in growing turkeys.

1. Large White male turkeys from a heavy commercial male-line were fed on 16 diets containing 4 concentrations of calcium (6, 10, 14 and 18 g/kg) and available phosphorus (3, 5, 7, 9 g/kg) in a 4 x 4 factorial experiment with three replicates (pens). Turkeys were weighed and food intakes recorded from 4 to 7, 8 to 10 and 11 to 13 weeks of age. 2. The diets containing 6 g/kg calcium and 5, 7 or 9 g/kg available phosphorus concentrations were associated with lower body weighs at 10 and 13 weeks of age. 3. Fewer than 6% of the turkeys had an abnormal gait at 13 weeks of age. 4. The optimum dietary concentrations were 10 g/kg of calcium and 3 g/kg of available phosphorus. It was concluded that these concentrations should be fed at least to 13 weeks of age. 5. Retentions of dietary calcium and phosphorus averaged 300 g/kg of intake. 6. Utilisation of dietary phytate ranged from 5 to 11 g/kg and it is recommended that organic phosphorus should be ignored in the formulation of diets for growing turkeys unless they are supplemented with a phytase enzyme.

Role of dietary calcium and available phosphorus in the aetiology of tibial dyschondroplasia in growing turkeys.

1. Large White male turkeys from a heavy commercial male-line were fed 16 diets containing 4 concentrations of calcium (6, 10, 14 and 18 g/kg) and available phosphorus (3, 5, 7 and 9 g/kg) in a 4 x 4 factorial experiment. There were three replicates (pens) of each treatment and the skeletal health, morphology and mineral status of 4 turkeys from each pen were assessed at 7, 10 and 13 weeks of age. 2. The prevalence of tibial dyschondroplasia increased after 7 weeks of age and was present in 50 and 71% of turkeys respectively at 10 and 13 weeks. The lesion was localised in the caudal aspect of the proximal tibiae. Dietary calcium and available phosphorus did not affect the prevalence of the lesion except in turkeys on the diet containing 6 g calcium/kg, where body weight and the incidence of tibial dyschondroplasia were low. 3. Histological investigation showed no evidence of rachitic changes. 4. Low dietary calcium was associated with lower tibial plateau angles at 10 and 13 weeks of age. Tibial torsion and the angle of rotation were not affected by dietary treatments or age. Tibial torsion and the angle of rotation were not affected by dietary treatments or age. 5. Increasing dietary calcium increased tibial radiodensity, cortical density and the widths of the cortex and proximal tibiotarsus. Radiodensities increased to 10 weeks and were significantly lower at 13 weeks of age. 6. Bone ash, calcium and phosphorus declined with age, particularly between 10 and 13 weeks, whereas bone calcium: phosphorus ratios were not affected by dietary treatment or age. 7. Dietary calcium was positively associated with blood calcium and calcium ion concentrations and was without effect on blood phosphorus. Available phosphorus was associated positively with increased blood phosphorus and lower calcium ion concentrations but had no effect on total calcium. Alkaline phosphatase activity was low at high concentrations of dietary calcium with low available phosphorus and there was higher activity on diets containing low calcium and high available phosphorus.

The safety of electrolytically induced hepatic necrosis in a pig model.

BACKGROUND: Electrolysis fulfils the criteria for an ideal treatment of patients with unresectable liver tumours. Previous studies in the rat and pig have shown that controlled necrosis can be safely produced by inserting platinum electrodes into normal liver' parenchyma and liver tumours. As with any new treatment it is mandatory to investigate the 'worst-case scenario' of inadvertent intravascular electrode placement in a large animal model before progressing to clinical trials. METHODS: Under ultrasound control in six pigs, electrodes were inserted into, or immediately adjacent to, an hepatic vein. An electrolytic 'dose' of 100 C was then administered and the evolution of the lesion was monitored using ultrasound. Venous blood was collected before and during the electrolysis to evaluate potential acid/base disturbances and animals were closely monitored during electrolysis and during their recovery until a full autopsy was performed 4-7 days after treatment. RESULTS: Gas bubbles were seen to enter the hepatic veins or interior vena cava during treatment in five of the six animals. There were no major complications as a consequence and all animals recovered and remained in a healthy state until they were killed. At autopsy one animal had complete thrombotic occlusion of the left hepatic vein. Otherwise, findings were normal. CONCLUSION: In the clinical setting, due to the use of ultrasound to guide electrode placement into the centre of a tumour, the electrodes should rarely juxtapose an hepatic vein. Nevertheless, in this extreme situation, electrolysis is surprisingly safe with only one major vascular occlusion and no morbidity or mortality.

Hippocampal Myc and p53 expression following transient global ischemia.

The proto-oncogene c-myc, and the tumor suppressor gene p53, encode proteins which function as transcriptional regulating factors governing cell proliferation, differentiation, and apoptosis. Recent evidence suggests that the delayed neuronal death which follows an episode of transient forebrain ischemia may involve apoptotic processes. We have therefore utilized immunohistochemistry to investigate the effects of transient global ischemia on neuronal expression of p53- and Myc-like immunoreactivities in the rodent forebrain 2, 12, 24, 48, and 72 h following reperfusion. Transient global ischemia (20 min), produced by four vessel occlusion (4-VO), initially elevated p53-like immunoreactivity in both CA1 and CA3 hippocampal subfields at 24 h of recirculation. However, distinct patterns of gene expression became evident in these regions at later time points. A pivotal difference was the persistence of ischemia-induced increases of p53- and Myc-like immunoreactivity in the CA1 region of the hippocampus. Unlike CA3 neurons where p53-like immunoreactivity subsided to basal levels by 48 h of survival, CA1 neurons continued to display increased p53-immunoreactivity 48 h post-ischemia, while Myc-like immunoreactivity was selectively elevated in CA1 neurons at this time point. Ischemia-induced increases in p53-like immunoreactivity were also detected in vulnerable regions of the amygdala, thalamus, and cortex 12 to 48 h after recirculation. Given that both p53 and Myc have been implicated in gene signalling pathways which mediate programmed cell death, our findings which demonstrate that 4-VO produces persistent elevations of p53- and Myc-like immunoreactivities in vulnerable neurons suggest that these proteins may also contribute to delayed neuronal death following an episode of transient forebrain ischemia.

D1-Receptor-related priming is attenuated by antisense-meditated 'knockdown' of fosB expression.

Administration of dopamine receptor agonists to rats with unilateral 6-hydroxydopamine lesions of the nigrostriatal pathway produce changes in the denervated striatum that enable a subsequent injection to elicit more vigorous circling. The molecular basis for this behavioural phenomenon, termed priming, is unknown. D1-receptor-related priming has been associated with a profound elevation of immediate-early gene (IEG) expression in the denervated striatum. Since immediate-early genes encode known transcriptional regulating factors, this observation has led to the suggestion that IEG induction may play a role in the gene signaling pathways which mediate priming. In the present study, we addressed the role of induction of the IEG fosB in dopamine agonist-induced priming by examining whether inhibition of the synthesis of FosB proteins (FosB and DeltaFosB) by intrastriatal delivery of an antisense oligonucleotide to fosB reduced apomorphine-induced priming. Intrastriatal delivery of an antisense, but not a random, oligonucleotide to fosB 18 and 6 h before apomorphine reduced the ability of this mixed D1¿D2-like receptor agonist to prime circling induced by the specific D1-like receptor agonist SKF 38393. Immunohistochemical analysis revealed that only the antisense oligonucleotide blocked apomorphine-induced increases in FosB-like immunoreactivity in the denervated striatum. In contrast, apomorphine-induced increases in JunB-, NGFI-A- and Fos2-16-like immunoreactivities were unaffected by either the antisense or random oligonucleotides, indicating that the antisense oligonucleotide attenuated apomorphine-induced priming by selectively blocking the synthesis of FosB proteins. Taken together, these findings suggest that fosB induction in the denervated striatum plays a role in mediating D1-receptor-related priming. Dopamine replacement therapy for Parkinson's disease is often complicated by the development of dyskinetic side effects. Results from the present study suggest that D1-receptor-mediated increases in fosB expression may be involved in those intracellular events responsible for the generation of these debilitating side effects.

On the mechanism of the effects of potassium restriction on blood pressure and renal sodium retention.

Dietary potassium restriction increases sodium and chloride retention, whereas potassium administration promotes both diuresis and natriuresis. In epidemiologic and clinical studies, potassium intake is inversely related to blood pressure and is lower in blacks than in whites. The present studies examined the mechanism by which potassium restriction fosters sodium conservation and the impact of race on this response. Twenty-one healthy black and white men and women ingested an isocaloric, potassium-restricted diet (20 mmol/d) containing 180 mmol/d of sodium with and without a potassium supplement (80 mmol/d) for 9 days on two occasions. Additionally, eight of these subjects ingested the same diets for 3 days followed by a water load to determine free water clearance before and during the early phase of dietary potassium restriction. During potassium restriction, mean arterial pressure (MAP) derived from 24-hour blood pressure measurements was higher (85.7 +/- 1.6 mm Hg v 82.0 +/- 1.3 mm Hg; P < 0.001), cumulative sodium excretion lower (984 +/- 59 mmol/d v 1,256 +/- 58 mmol/d; P < 0.001), and weight greater (71.1 +/- 2.1 kg v 69.3 +/- 2.2 kg; P < 0.001). Blacks displayed no greater increase in MAP, although they excreted less sodium overall and less potassium on the potassium-supplemented diet. After a water load, minimum urine osmolality (Uosm) was lower (53.0 +/- 3.0 mOsm/L v 65.6 +/- 3.5 mOsm/L; P = 0.01) and free water clearance greater (4.44 +/- 0.59 mL/min v3.72 +/- 0.58 mL/min; P = 0.009) during potassium restriction. In conclusion, in healthy, normotensive subjects, potassium restriction was associated with an increase in blood pressure and volume expansion effected by increased renal sodium and chloride retention. Potassium restriction was also associated with increased free water clearance and enhanced diluting capacity consistent with augmentation of Na+, K+:2Cl- cotransporter activity in the thick ascending limb of Henle. This mechanism may play an important role in the renal adaptation required for potassium conservation, but at the expense of sodium chloride retention and an elevation in blood pressure.

Distribution of neuronal apoptosis inhibitory protein-like immunoreactivity in the rat central nervous system.

We have recently shown that spinal muscular atrophy (SMA), an autosomal recessive disorder characterized by motor neuron loss, is associated with deletion of a gene that encodes the neuronal apoptosis inhibitory protein (NAIP). In the present study, we have examined the distribution of NAIP-like immunoreactivity (NAIP-LI) in the rat central nervous system (CNS) by using an affinity-purified polyclonal antibody against NAIP. In the forebrain, immunoreactive neurons were detected in the cortex, the hippocampus (pyramidal cells, dentate granule cells, and interneurons), the striatum (cholinergic interneurons), the basal forebrain (ventral pallidum, medial septal nucleus, and diagonal band), the thalamus (lateral and ventral nuclei), the habenula, the globus pallidus, and the entopenduncular nucleus. In the midbrain, NAIP-LI was located primarily within neurons of the red nucleus, the substantia nigra pars compacta, the oculomotor nucleus, and the trochlear nucleus. In the brainstem, neurons containing NAIP-LI were observed in cranial nerve nuclei (trigeminal, facial, vestibular, cochlear, vagus, and hypoglossal nerves) and in relay nuclei (pontine, olivary, lateral reticular, cuneate, gracile nucleus, and locus coeruleus). In the cerebellum, NAIP-LI was found within both Purkinje and nuclear cells (interposed and lateral nuclei). Finally, within the spinal cord, NAIP-LI was detected in Clarke's column and in motor neurons. Taken together, these results indicate that NAIP-LI is distributed broadly in the CNS. However, high levels of NAIP-LI were restricted to those neuronal populations that have been reported to degenerate in SMA. This anatomical correspondence provides additional evidence for NAIP involvement in the neurodegeneration observed in acute SMA.

Intra- and interexaminer reliability of the chiropractic biophysics lateral lumbar radiographic mensuration procedure.

OBJECTIVE: To determine the intra- and interexaminer reliability of a specific method of mensuration commonly used to evaluate the positional configuration of the lumbopelvic spine viewed on lateral lumbar radiographs. DESIGN: A blind, repeated-measures design was used. Lateral lumbopelvic radiographs were presented to each of three examiners in random order. Each film was marked and measurements were recorded. The films were cleaned of all markings and randomized again for a second run by each examiner. Each examiner's measurements were unavailable to the other examiners. SETTING: Private, primary-care chiropractic clinic. MAIN OUTCOME MEASURES: Anterior/posterior thoracic translation in millimeters, Ferguson's sacral-plane angle to horizontal, arcuate line angle to horizontal, L1 to L5 absolute rotation angle and four relative rotation angles for L1-L2, L2-L3, L3-L4 and L4-L5. Intra- and interrelibility of the three radiographic examiners were analyzed. RESULTS: Intraexaminer reliability for (a) L1-L5 absolute rotation angle was .98, with confidence intervals included in the range of 0.95-0.99, (b) anterior/posterior thorax translation [+/- Sz] was .97-.99, with confidence intervals included in the range of 0.94-1.00, (c) arcuate angle (AA) .40-.81, with confidence intervals included in the range of 0.07-0.90, (d) Ferguson's angle (FA) was .91-.97, with confidence intervals included in the range of 0.82-0.98, (e) relative rotation angle reliability ranges were L1-L2, .84-.94; L2-L3, .80-.85; L3-L4, .78-.89; L4-L5, .87-.92. Interexaminer reliabilities for the three examiners ranged from .66-.98. CONCLUSION: With the exception of the arcuate angle measurement, the reliabilities for all other measurements were at least .78. Those measurements with reliabilities approaching .80 or better would be considered accurate enough for use in future clinical studies. The arcuate angle measurement may have been least reliable because of the subjective nature of the method of affixing a best-fit line to a radiographic landmark that often takes on the appearance of a mild curvature. Establishing reliability is an important first step toward evaluating these and other similar radiographic measurements that have yet to be examined for their validity.

The identification of potential aeroallergen/irritant(s) from oilseed rape (Brassica napus spp. oleifera): volatile organic compounds emitted during flowering progression.

Volatile organic compounds emitted by growing intact oilseed rape plants have been detected using an entrainment apparatus enabling volatile headspace analysis by thermal desorption coupled to capillary gas chromatography-mass spectrometry. In total, 22 volatile compounds were identified as being emitted during the flowering period. The main constituents were alpha-farnesene (a sesquiterpene); beta-myrcene (a monoterpene); linalool (a monoterpene alcohol) and the 'green leaf' volatile (E)-3-hexen-1-ol acetate. These compounds constituted between 50 and 87% (mean 68%) of the total volatiles emitted in all of the entrainments carried out with flowering oilseed rape plants. The remaining constituents consisted of a range of compounds including other terpenoids, the characteristic 'green leaf' volatile (E)-3-hexen-1-ol, short chain alcohols and ketones, organic sulphides and nitrogen-containing compounds. These were generally present as minor constituents but some plant entrainments revealed that higher relative amounts could be emitted. This was particularly apparent for dimethyl disulphide, 3-methyl-2-pentanone, 3-hydroxy-2-butanone, sabinene, isomyrcenol and (E)-3-hexen-1-ol. The possible role of the 22 compounds in respiratory mucosa and conjunctiva irritation associated with airborne releases from oilseed rape is discussed.

The efficacy of cervical extension-compression traction combined with diversified manipulation and drop table adjustments in the rehabilitation of cervical lordosis: a pilot study.

OBJECTIVE: To experimentally investigate the effect of cervical extension-compression traction combined with diversified chiropractic manipulation and drop table adjusting in establishing or increasing cervical lordosis. DESIGN: Blinded, before and after trial with pre- and postlateral cervical radiographic measurement. SETTING: Primary care private chiropractic clinic in Saugus, MA. SUBJECTS: A) Control group--convenience sample who had no health care for 10-14 wk, 30 persons. B) Treatment group 1, nonrandomized control trial, 35 persons, whose pre- and postlateral cervical radiographs were taken 10-14 wk apart and whose radiographs clearly depicted C1 through C7. C) Treatment group 2, nonrandomized control trial, 30 persons, whose pre- and postlateral cervical radiographs were taken 10-14 wk apart and whose radiographs clearly depicted C1 through C7. INTERVENTIONS: Treatment group 1: diversified spinal manipulation, drop table adjustments and cervical extension-compression traction five times per week for 10-14 wk (12 wk +/- 2). Treatment group 2: diversified spinal manipulation and drop table adjustments five times per week for 10-14 wk (12 wk +/- 2). MAIN OUTCOME MEASURES: Anterior head translation millimeters, C2 to C7 absolute rotation angle, angle of C1 to horizontal (atlas plane angle), five relative rotation angles (C2-3, C3-4, C4-5, C5-6, C6-7) and qualitative classification of lordotic configuration. RESULTS: No statistically significant changes existed between the pre- and posttests for the control group except in the C6-7 relative rotation angle. In the treatment group 1, statistically significant differences were found in all X-ray markings. Twenty-nine of 35 members have a lordosis after treatment compared to 11 of 35 before treatment. The C2 to C7 angle changed an average 13.2 degrees, C1 to horizontal changed an average 9.8 degrees, the anterior head translation reduced an average of 6.8 mm, the average relative rotation angle changed: C2-3: 3.1, C3-4: 5.5, C4-5: 4.80, C5-6: 2.7 and C6-7: 1.1. In the treatment group 2, no statistically significant changes existed between the pre- and posttests except atlas angulation to horizontal which increased an average of 3.0 degrees. CONCLUSIONS: A transformation to a lordotic configuration or increase in lordotic configuration occurred and was measured in the majority of treatment group 1 subjects, while no change in the control group and essentially no change in treatment group 2 was measured. Extension-compression traction combined with diversified chiropractic manipulation and drop table adjusting procedures may improve or partially reestablish the cervical lordosis in 10-14 wk of daily care.

Hypodipsic hypernatremia in a dog with defective osmoregulation of antidiuretic hormone.

Hypernatremia was detected in a dog that was evaluated because of seizures. During hospitalization, the dog was fully conscious and remained hypernatremic when drinking voluntarily and when water was added to the food. Urine volume increased and urine osmolality decreased during an infusion of hypertonic saline (2.5% NaCl) solution, despite development of progressive hyperosmolality. There was no correlation between plasma antidiuretic hormone concentration and osmolality during the infusion study. The dog released antidiuretic hormone normally after nonosmotic stimulation (ie, apomorphine administration). These findings allowed a diagnosis of hypodipsic hypernatremia caused by destruction of hypothalamic osmoreceptors. At necropsy, there was hydrocephalus, atrophy of the septum pellucidum, and neuraxonal dystrophy of the cuneate nuclei. The underlying neurologic disease responsible for the CNS lesions could not be determined, but hydrocephalus may have led to pressure atrophy in the region of the hypothalamus that contains osmoreceptors.