Mental health and debt: challenges for knowledge, practice and identity.

People with mental health problems (MHPs) in Britain are nearly three times more likely to report debt compared with individuals without similar conditions. With one-in-four respondents with MHPs reporting personal debt, this may be equivalent to eight or nine clients in the recommended national community mental health nurses' (CMHNs) caseload of 35. Although client debt is not a new problem for CMHNs, it can pose significant difficulties for client well-being and nursing practice. This paper reviews the published literature on debt and mental health, then considers three of the challenges that client debt can present to: (1) nursing knowledge--moving away from understandings of client debt based on crisis, and towards those focused on process and prevention; (2) nursing practice--reworking the collaborative relationship between CMHNs and external debt advice agencies; and (3) nursing identity--managing the role conflicts that engaging with client debt can bring. The paper concludes by contending that nurses should raise and monitor debt issues among clients, but cannot be expected to become proxy 'debt advisors', with CMHNs being encouraged to increasingly collaborate with debt advisors (rather than simply referring on clients).

The ISABEL user survey.

ISABEL is a web-based clinical decision-support system for use by health care professionals. The Web site has been developed by the ISABEL Medical Charity. The system has come to the attention of the Department of Health, which is examining its potential effectiveness in the wider clinical context and exploring options for promoting its wider use in the NHS. The objectives of the work reported here were to review the existing use of ISABEL and to identify impediments to its development. A questionnaire was sent by e-mail to selected users of the system. Based on an analysis of the results (n=518), we found ISABEL to be a useful tool with many users. We believe that there is evidence of its success sufficient to support its continued availability and development. However, the largest hurdles to its increased use are systemic ones within the NHS and the way services are delivered.

Rapid habituation of hippocampal serotonin and norepinephrine release and anxiety-related behaviors, but not plasma corticosterone levels, to repeated footshock stress in rats.

Prior stress exposure is known to alter the activation response to a subsequent stressor. In the present study, we examined neurochemical, neuroendocrinological, and behavioral correlates of short-term adaptation to homotypic stressors administered 60 min apart. An initial electric footshock significantly induced extracellular levels of both serotonin (5-HT) and norepinephrine (NE) in the rat hippocampus (650% and 200% above baseline, respectively), as measured by in vivo microdialysis. A rapid habituation in this response was evident in the inability of a second footshock to evoke similar increases. In contrast, the hypothalamic-pituitary-adrenal (HPA) response was augmented further after the second shock session: plasma corticosterone (CORT) levels were 18.1, 316.5, and 441.6 mg/ml in nonstressed, one-footshock-, or two-footshock-treated rats, respectively. In a social interaction paradigm, rats subjected to a single footshock showed several fear- and anxiety-related behaviors such as increases in freezing and decreases in rearing and active approach for social interaction. Exposure to a second footshock completely blocked the freezing response and restored rearing behavior without affecting the disruption in social interactions. Taken together, these data raise the possibility that neurochemical and neuroendocrine adaptations to short-term homotypic stressors differentially contribute to expression of different fear and anxiety-like responses in the rat.

Tumor suppressor protein p53 mRNA and subcellular localization are altered by changes in cellular copper in human Hep G2 cells.

Copper toxicity causes hepatic damage that can lead to the development of hepatocarcinoma. Similarly, copper deficiency has been reported to increase hepatocyte tumorigenesis. Thus, the objective of this work was to explore the role of copper toxicity and deficiency in the regulation of the tumor suppressor protein p53. Using Northern analysis, Western analysis, immunocytochemistry and the human hepatoma cell line Hep G2, this work showed that elevations in hepatocyte copper consistent with Wilson's disease (5.7-fold increase) induced p53 mRNA and confirmed that copper toxicity is correlated with apoptotic cell death. However, Western analysis and immunocytochemistry showed that post-transcriptional mechanisms are a significant part of the process, with p53 translocation from the cytosol into the nucleus of copper-treated cells. Treatment of Hep G2 cells with increasing concentrations of the copper chelator tetraethylenepentamine (TEPA, 0-50 micromol/L, 48 h) reduced cellular copper and increased mean p53 mRNA abundance by over fourfold with nuclear translocation of the wild-type protein. However, TEPA treatment did not result in a loss of cell viability or appear to induce apoptosis.

A role for linoleic acid in erythrocytes infected with Plasmodium berghei.

Unesterified fatty acids were measured in mouse erythrocytes infected either with chloroquine-susceptible (CS) or with chloroquine-resistant (CR) lines of Plasmodium berghei. This work was undertaken to identify candidates for the lipid involved in ferriprotoporphyrin IX (FP) polymerization. Linoleic, oleic, palmitic, and stearic acids were quantified by gas chromatography/mass spectrometry. In total, they increased 4-fold with CS infections and 6-fold with CR infections. Treating infected mice with chloroquine did not affect the amounts of unesterified fatty acids in erythrocytes. Of the four fatty acids, only linoleic acid increased disproportionately to the total. It increased 16-fold for the CS line and 35-fold for the CR line. The method could detect monoglycerides but they were below the limit of detection. It could not detect diglycerides, triglycerides or phospholipids. Triglycerides and phospholipids have been tested previously, however, and found to be ineffective at promoting FP polymerization. Therefore, other than linoleic acid, the lipids most likely to be involved in FP polymerization are diglycerides. We tested dilinoleolyglycerol in the present work and found it to be an effective promoter of FP polymerization. These results suggest that linoleic acid or a diglyceride containing it has the critical role of promoting FP polymerization in malaria parasites.

Salt effects on ionization equilibria of histidines in myoglobin.

The salt dependence of histidine pK(a) values in sperm whale and horse myoglobin and in histidine-containing peptides was measured by (1)H-NMR spectroscopy. Structure-based pK(a) calculations were performed with continuum methods to test their ability to capture the effects of solution conditions on pK(a) values. The measured pK(a) of most histidines, whether in the protein or in model compounds, increased by 0.3 pH units or more between 0.02 M and 1.5 M NaCl. In myoglobin two histidines (His(48) and His(36)) exhibited a shallower dependence than the average, and one (His(113)) showed a steeper dependence. The (1)H-NMR data suggested that the salt dependence of histidine pK(a) values in the protein was determined primarily by the preferential stabilization of the charged form of histidine with increasing salt concentrations rather than by screening of electrostatic interactions. The magnitude and salt dependence of interactions between ionizable groups were exaggerated in pK(a) calculations with the finite-difference Poisson-Boltzmann method applied to a static structure, even when the protein interior was treated with arbitrarily high dielectric constants. Improvements in continuum methods for calculating salt effects on pK(a) values will require explicit consideration of the salt dependence of model compound pK(a) values used for reference in the calculations.

Reliability and validity of disability questions for US Census 2000.

OBJECTIVES: We investigated the validity and proxy reliability of 7 new disability questions from the 2000 US census ("Census 2000"). METHODS: A total of 131 people with disabilities and their proxies from St Louis, Mo, and Massachusetts were interviewed, and responses were compared for concordance. Responses also were compared with responses to questions from the Behavioral Risk Factor Surveillance System (BRFSS) and the Activities of Daily Living (ADL) instrument. RESULTS: Overall, proxies reported more impairment than did people with disabilities, and agreement was low (kappa = 0.24-0.55). Concordance was moderate between the census questions and their BRFSS and ADL counterparts. CONCLUSIONS: The Census 2000 questions may not provide an accurate profile of disability in America.

Origins of an epidemic: the methodological and political emergence of rapid assessment.

The recent emergence of rapid assessment as a public health tool in the drug and alcohol field has been a relatively ahistorical process. The lack of such an explicit historical biography is understandable - the findings and impact of rapid assessment have rarely made their way into mainstream journals. However, its continued absence presents the manifest danger of an inward-looking field. This paper describes the development of rapid assessment during the past two decades, with a detailed focus on the emergence of rapid assessment in the drug and alcohol field. This focuses on the central role played by international agencies during the 1980s and 1990s, and the development of rapid methodologies by the World Health Organization to prevent epidemics of HIV among injecting drug users, and the use of rapid methodologies by the United Nations International Drug Control Programme to instruct drug policy reform. The paper also describes key events in other fields including: the emergence of the first formal rapid methodologies in the late 1970s, and the production of the first formal guidelines on conducting rapid assessment during the mid-1980s. The paper concludes by highlighting common challenges that rapid methodologies have faced throughout their history.

Effect of altered thyroid hormone status on rat brain ferritin H and ferritin L mRNA during postnatal development.

The iron binding protein ferritin is a heterogeneous mix of 24 heavy (H) and light (L) subunits. The H subunit is associated with iron utilization, while the L subunit is responsible for iron storage. Examination of the developmental pattern of mRNA abundance in rat brain revealed that ferritin L mRNA is highest at birth and declines during the first postnatal week. A similar decline was seen in ferritin H mRNA, but was followed by an increase in ferritin H mRNA in the second postnatal week which continued through postnatal day 21. The pattern of H mRNA regulation is similar to that in previous reports of total ferritin protein in the developing rat brain and is consistent with the fact that brain ferritin is predominately ferritin H. The effect of thyroid hormone on the developmental regulation of ferritin mRNAs was examined by the subcutaneous injection of a single dose of exogenous thyroxine (T(4); 2 microg/g) on postnatal day 1. Hypothyroidism was induced in pregnant dams with propylthiouracil (PTU; 0.05% in drinking water) from gestational day 7. Northern analysis from postnatal days 2-21 showed that T(4) increased ferritin H mRNA throughout development, while ferritin L mRNA was decreased compared to age-matched controls. PTU treatment decreased ferritin H and increased L mRNA in the later stages (days 14-21) of development. Given the distinct functions of ferritin H and L this suggests a role for thyroid hormone in the ability of the brain to regulate stored vs. utilizable iron during critical periods of development.

Measurement and manipulation of the partial pressure of oxygen in the rat anterior chamber.

PURPOSE: To measure the partial pressure of oxygen in the anterior chamber of the rat eye under a variety of physiological conditions. METHODS: Polarographic oxygen electrode measurements were made in methoxyflurane-anesthetized Wistar or Sprague-Dawley rats. After ketamine-xylazine or pentobarbital induction, animals were artificially ventilated with a variety of gas mixtures; gases were directed over the corneal surface during measurement of the partial pressure of oxygen in the middle of the pupil at the surface of the lens. RESULTS: The partial pressure of oxygen in the anterior chamber of the rat eye was measured as 63 +/- 9 mm Hg (mean +/- S.D. ). Breathing 100% oxygen and delivery of 100% oxygen to the cornea additively increased aqueous humor oxygen partial pressure to levels above 279 +/- 45 mm Hg with the greatest increase coming from inhaled 100% oxygen. Conversely, inhalation and subsequent transcorneal delivery of 10% oxygen reduced levels to 22 +/- 11 mm Hg. CONCLUSIONS: These results suggest that the partial pressure of oxygen in the anterior chamber is sensitive to the environment in contact with the cornea. In the rat eye, the delivery of oxygen to the anterior chamber via transcorneal diffusion may be more significant than for larger animals.

Regulation of mitochondrial cytochrome b mRNA by copper in cultured human hepatoma cells and rat liver.

Copper overload and deficiency are known to cause morphological and functional mitochondrial abnormalities. The reverse transcriptase-polymerase chain reaction (RT-PCR)-based method of differential display of mRNA was used to identify genes with altered expression in cultured human hepatoma cells (Hep G2) exposed to increasing concentrations of copper (0-100 microM, 24 h). Copper regulation of a cloned PCR product, identified as the gene for the mitochondrially encoded cytochrome b, was confirmed by Northern analysis and in situ hybridization. Copper toxicity increased cytochrome b mRNA abundance up to 3.6-fold, and copper chelation reduced it by 50%. Hepatic cytochrome b mRNA was also increased in rats fed a high-copper diet. Thapsigargin treatment resulted in a significant increase in cytochrome b mRNA, suggesting that an increase in intracellular calcium may be involved in the mechanism of copper action. Furthermore, although cyclohexamide (CHX) alone did not increase cytochrome b mRNA, the addition of CHX and copper resulted in a sixfold increase. These data suggest a role for cytochrome b in the response to increases or decreases in hepatic copper.

Regulation of metallothionein-3 mRNA by thyroid hormone in developing rat brain and primary cultures of rat astrocytes and neurons.

Metallothionein-3 (MT-3) is a brain specific member of the MT family. Unlike other members of this family, MT-3 has been shown to act as a neuronal growth inhibitory factor. MT-3 mRNA abundance increases throughout the developmental period, reaching adult levels by postnatal day 21. The role of thyroid hormone in the developmental regulation of MT-3 mRNA was tested because thyroid hormone is known to regulate brain gene expression. Furthermore, gestational hypothyroidism results in developmental brain abnormalities. Hypothyroidism was induced in pregnant dams by the administration of PTU from gestational day 7, resulting in a 4- to 6-fold increase in pup MT-3 mRNA abundance on the day of birth (day 0) and on postnatal day 3. Normal pups did not reach this level of brain MT-3 mRNA until postnatal day 21. Administration of thyroxine (T(4), 2 microg/g) to pups on postnatal day 1 or day 20 resulted in a decrease in MT-3 mRNA abundance on postnatal day 21, regardless of when the injection was given. Furthermore, addition of T(4) to primary cultures of brain (olfactory bulb) astrocytes and neurons from 4-day-old rats resulted in a significant decrease in MT-3 mRNA in 24 h. Given the neuronal growth inhibitory function of MT-3, these data suggest that MT-3 may play a role in the CNS-related consequences of hypo- and hyperthyroidism during development.

Involvement of lipids in ferriprotoporphyrin IX polymerization in malaria.

Approximately 70% of the initial ferriprotoporphyrin IX polymerizing activity in cell-free preparations of erythrocytes infected with Plasmodium berghei was recovered in a chloroform extract. No polymerizing activity remained in the residue. In studies to identify substances that promote FP polymerization, arachidonic, linoleic, oleic, and palmitoleic acids, 1-mono- and di-oleoylglycerol, and the detergents, SDS, Tween 80, and n-octyl-glucopyranoside, were active. Tri-oleoylglycerol, cholesterol, di-oleoylphosphatidylethanolamine, and stearic and palmitic acids were inactive. The model lipid, mono-oleoylglycerol (250 nmol), co-precipitated with FP from a 0.09 M acetate medium at pH 5 and promoted the polymerization of 215 nmol (61%) of the ferriprotoporphyrin IX in the precipitate during a 24-h incubation at 37 degrees C. Polymerization was maximal at pH 5, it was approximately linear for 2 h, and it continued at a decreasing rate for 24 h. The polymer contained exclusively ferriprotoporphyrin IX (97+/-1.3%, mean+/-S.E., n=4) and exhibited the solubility and the electronic absorption and infrared spectral characteristics of the sequestered ferriprotoporphyrin IX of hemozoin. Detergents presumably promote polymerization in an acid medium by helping to dissolve monomeric FP. We suggest that unsaturated lipids co-precipitate with FP in the parasite's acidic food vacuole and also dissolve sufficient monomeric FP to allow polymerization.

Developmental regulation of hepatic ceruloplasmin mRNA and serum activity by exogenous thyroxine and dexamethasone.

Ceruloplasmin (Cp) is a copper-dependent oxidase with roles that include the regulation of iron metabolism, participation in the acute-phase response to inflammation, and antioxidant systems. Although developmental increases in hepatic Cp gene expression and serum activity have been described, the molecular mechanisms that are responsible for this regulation are not fully understood. The studies described here explored the possible role of glucocorticoids and thyroxine (T4) in the early neonatal development of Cp by the administration of these hormones on postnatal Day 1 (24 hr after birth), and the measurement of both hepatic Cp mRNA and serum activity through postnatal Day 10. Administration of the synthetic glucocorticoid hormone, dexamethasone (2 micrograms/g body wt), resulted in an increase in Cp mRNA on Days 3-7 that was accompanied by an increase in serum Cp activity that reached statistical significance at Day 10. Exogenous T4 (2 micrograms/g body wt) significantly increased Cp mRNA 24 hr after administration. Serum Cp activity was also significantly elevated by the early neonatal administration of T4. Furthermore, gestational hypothyroidism resulted in a significant decrease in Cp activity after postnatal Day 3. These data suggest a role for thyroid hormone and possibly glucocorticoids in the normal developmental regulation of Cp.

Regulation of neuropeptide Y mRNA and peptide concentrations by copper in rat olfactory bulb.

Neuropeptide Y is highly abundant in both the peripheral and central nervous systems and is known to have diverse functions including regulation of feeding behavior, blood pressure, circadian rhythms, reproductive behavior and the response to stress. Northern analysis showed that copper deficiency increased brain NPY mRNA abundance particularly in the olfactory bulb (OB). These increases were not accompanied by alterations in food intake or blood pressure. After 4 weeks of a copper-restricted diet, OB copper concentrations decreased to 44% of control and NPY mRNA increased 1.5-fold. Addition of a copper chelator to the restricted diet, resulted in a two-fold increase in OB NPY mRNA over copper adequate controls. These results were confirmed in primary cultures of OB neurons suggesting that the regulation of NPY mRNA is at the level of the bulb rather than by a hormonal or other copper-regulated factor external to the OB. Immunoreactive NPY (IR-NPY) levels were not, however, increased following the 4 weeks of copper deficiency. Addition of the chelator resulted in a 1.4-fold increase in IR-NPY that, while statistically significant, was not proportional to the two-fold increase in NPY mRNA in the same study. This may suggest that copper deficiency inhibits the translational mechanisms responsible for the synthesis of NPY or that NPY is exported from the bulb in copper deficiency.

HIV infection associated with drug injecting in the newly independent states, eastern Europe: the social and economic context of epidemics.

AIMS: We review recent trends in HIV associated with injecting drug use (IDU) in the Newly Independent States (NIS) in eastern Europe, including Belarus, Moldova, Russia, Ukraine, and Kazakhstan in central Asia. We aim to draw attention to the social and economic "risk environments" in which rapid HIV spread among IDUs has occurred. METHODS: Findings draw on centrally registered HIV surveillance data, published research studies and assessment reports funded by international development agencies. FINDINGS: Since 1995, there is evidence of rapid HIV spread in Belarus, Kazakhstan, Moldova, Russia and Ukraine, with estimates suggesting between 50% and 90% of new HIV infections among IDUs. At the same time, there have been rapid increases in the incidence of syphilis and declines in health and welfare status, including outbreaks of diphtheria, tuberculosis and cholera. Findings emphasize the potential influence of the social and economic context in creating the "risk environments" conducive to HIV and epidemic spread. Key factors include: rapid diffusions in IDU; population migration and mixing; economic transition and decline; increasing unemployment and impoverishment; the growth of informal economies; modes of drug production, distribution and consumption; declines in public health revenue and infrastructure; and political, ideological and cultural transition. CONCLUSIONS: An understanding of the social and economic contexts mediating HIV spread is a prerequiste to identifying the environmental "pre-conditions" of epidemic outbreaks, and thus also, for predicting and preventing HIV transmission. The "risk environment" may influence the efficacy of individual and community-level HIV prevention and highlights the concomitant urgency for interventions targeting social and environmental change.