Antidepressant drug consumption and public health indicators in Italy, 1955 to 2000

OBJECTIVE: This study investigated the impact of the increasing consumption of selective serotonin reuptake inhibitors (SSRIs) and newer anti-depressants on the following public health indicators: (1) suicide rates, (2) proportion of completed suicides by poisoning with solid or liquid substances, and (3) hospital admissions for depression and proportion of admissions for depression that were first admissions. METHOD: Data collected by IMS Health on antidepressants dispensed in Italy from 1983 to 2000 were obtained from the Italian Ministry of Health, while data on suicide deaths from 1955 to 2000 were obtained from the Italian National Institute of Statistics. RESULTS: In Italy from 1983 to 2000, the use of tricyclic antidepressants remained substantially stable, and the use of SSRIs and newer agents dramatically increased. In contrast, suicide rates for males decreased from 1955 to 1974 and subsequently increased, reaching a peak in 1985 and then declining. In females, suicide rates remained substantially stable until 1978. A subsequent increase occurred up to 1985, followed by a steady decline. Suicide by poisoning using solids or liquids dropped by nearly 50% from 1986 to 2000. Admissions to the hospital for depression showed an erratic pattern; however, no decline was observed. No change was observed in the rate of first admissions for depression. CONCLUSION: Despite a reduction in suicides by poisoning using solids or liquids, the analysis of long-term trends in suicide did not suggest that increases in antidepressant prescribing lie behind recent reductions in population suicides. Furthermore, in Italy, newer antidepressants had no impact on the total number of admissions for depression or on the proportion of all admissions that were first admissions.     

Barriers to caregiver administration of pain medication in hospice care

Barriers to adequate pain management in hospice and palliative care settings are an important area of investigation. In this study, a Caregiver Pain Medicine Questionnaire (CPMQ) was developed and psychometrically tested. The CPMQ is a 22-item self-report instrument that measures concern about reporting pain, concern about administering analgesics, and difficulty administering analgesics. One hundred fifty-one caregivers of patients admitted to three Chicagoland hospice agencies participated; these individuals were family members, hired caregivers in the home, or staff nurses in skilled care facilities. While only a small percentage of the caregivers expressed concern about communicating information about the patient's pain, more than a quarter were concerned about addiction, tolerance, and side effects from medications. A fourth of the caregivers had difficulty administering medications because of fear of doing something wrong and difficulty deciding which or what amount of medications to give. Male caregivers and hired caregivers had greater concerns, both about reporting information about the patient's pain and administering medications. Greater concerns were also evident among less educated caregivers, caregivers who worked in blue-collar jobs, and caregivers who were homemakers or retired. Concerns of caregivers in the home were significantly greater than staff nurse caregivers in skilled care facilities only in the belief that pain could not be controlled and concern about addiction. Caregivers who had greater concern about addiction and tolerance, and more difficulty administering medications, rated the patient's pain as less completely controlled. These findings remind hospice staff members of the importance of assessing specific caregiver concerns about medication administration and devising appropriate strategies to address them.     

Type II Benign Osteopetrosis (Albers-Schönberg Disease) Caused by a Novel Mutation in CLCN7 Presenting with Unusual Clinical Manifestations

A 16-year-old male patient with type II autosomal dominant benign osteopetrosis (ADO) was genotyped and found to harbor a novel mutation in exon 25 of the gene encoding for the osteoclast-specific chloride channel, CLCN7, inherited from the father, who was asymptomatic. The patient had normal biochemical findings and acid-base balance, except for increased serum levels of creatine kinase, lactic dehydrogenase, and the bone formation markers bone alkaline phosphatase isoenzyme, osteocalcin and N-terminal type I collagen telopeptide/creatinine ratio. Unusual generalized osteosclerosis was observed together with a canonical increase in vertebral and pelvis bone mass. An affected first grade cousin presented with normal biochemical findings and a milder osteosclerotic pattern of the pelvis. At the cellular level, cultured osteoclasts from the patient showed increased motility, with lamellipodia, membrane ruffling and motile pattern of podosome distribution, all of which could have contributed to functional impairment of bone resorption. The present report documents a novel mutation of the CLCN7 gene causing osteopetrosis in a radiologically uncertain form of the diseases, with apparent incomplete penetrance.     

Lichen sclerosus of the male genitalia and urethral stricture diseases

INTRODUCTION: The true incidence of urethral involvement in patients with genital lichen sclerosus (LS) is unknown. We review the epidemiology and discuss the pathogenesis of LS and urethral stricture diseases. MATERIALS AND METHODS: During the period 1991-2002, of 925 patients who underwent urethroplasty for anterior urethral stricture, 130 patients (14%) received the diagnosis of LS. In all patients with LS the histology was re-examined to confirm the clinical diagnosis. Retrograde and voiding urethrography was used to establish urethral involvement in the disease. RESULTS: In 106 patients (82%) the histology provided the classical features of LS, and 24 patients (18%) showed some histological variations. In 49 patients (37%) the LS involved the pendolous urethra (meatus-navicularis-penile), and in 53 cases (41%) a panurethral stricture was evident. CONCLUSIONS: LS urethral involvement appears to be a much more common and extensive disease than previously reported, and requires particular care in its early diagnosis.     

Cloning, pharmacological characterisation and distribution of the rat G-protein-coupled P2Y(13) receptor

The human P2Y(13) receptor is a new receptor characterized by coupling to Gi, responsiveness to adenine di-phospho-nucleotides and blockade by the P2Y antagonist AR-C69931MX. The mouse P2Y(13) ortholog has also been reported. Here we report, for the first time, the cloning of rat P2Y(13) receptor, its pharmacological analysis and tissue distribution. Rat P2Y(13) is 79% and 87% identical to human and mouse P2Y(13) receptors, respectively. Expression of rP2Y(13) receptor in 1321N1 cells induced the appearance of responses to the typical P2Y(13) receptor agonists ADP and 2MeSADP, as detected by stimulation of [(35)S]GTPgammaS binding. Agonist activities were higher in cells transfected with rP2Y(13) receptor in the presence of the Galpha(16) subunit; in all cases agonist effects were abolished by pertussis toxin pre-treatment. At variance from both human and mouse receptors, ADP was more potent than 2MeSADP. Other nucleotides and sugar-nucleotides were ineffective. Both in the absence and presence of Galpha(16), activation of rP2Y(13) receptor by ADP and 2MeSADP was completely inhibited by nM concentrations of AR-C69931MX. In contrast, no inhibition of rP2Y(13) receptor was induced by the selective P2Y(1) receptor antagonist MRS2179. rP2Y(13) receptor showed highest expression levels in spleen, followed by liver and brain (with particularly high levels in cortex and striatum as reported in man), suggesting important roles in the nervous and immune systems. Expression levels comparable to those of the other cloned P2Y receptors were found in primary rat astrocytes, indicating a possible role in reactive astrogliosis. Hence, rat P2Y(13) receptor displays several similarities but also interesting differences with its human and mouse orthologs, that will have to be taken into account when characterizing the pathophysiological roles of this receptor in the rat animal models.     

Synthesis and antibacterial evaluation of oxazolidin-2-ones structurally related to linezolid

Compounds structurally related to the known antimicrobial drug linezolid were selected in order to evaluate the influence of electron-withdrawing properties and altered geometric features as a result of the N-substituent modification. After a preliminary study of molecular modeling, cinnamoyl-, pyridin- and pyrimidinoxazolidin-2-ones were synthesized. None of the new compounds showed antibacterial activity.     

1,2,4-triazolo[4,3-a]quinoxalin-1-one moiety as an attractive scaffold to develop new potent and selective human A3 adenosine receptor antagonists: synthesis, pharmacological, and ligand-receptor modeling studies

In the past few years much effort in our laboratory has been directed toward the study of adenosine receptor antagonists, and recently we focused our attention on 2-aryl-1,2,4-triazolo[4,3-a]quinoxaline-1,4-diones and 2-aryl-1,2,4-triazolo[4,3-a]quinoxalin-4-amino-1-ones, some of which were potent and/or selective A(3) receptor antagonists. In the present paper, a new series of triazoloquinoxaline derivatives is described. Most of the new compounds, biologically evaluated in radioligand binding assays at bovine (b) A(1) and A(2A) and at human (h) A(1) and A(3) adenosine receptors, showed high hA(3) adenosine receptor affinity and selectivity. In particular, 2-(4-nitrophenyl)-1,2,4,5-tetrahydro-1,2,4-triazolo[4,3-a]quinoxaline-1,4-dione (1), also tested at the hA(2A) ARs, shows the best binding profile with a high hA(3) affinity (K(i) = 0.60 nM) and strong selectivity vs hA(1) and vs hA(2A) receptors (both selectivity ratios greater than 16 600). To interpret our experimental results, we decided to theoretically depict the putative transmembrane binding motif of our triazoloquinoxaline analogues on hA(3) receptor. Structure-activity relationships have been explained analyzing the three-dimensional structure of the antagonist-receptor models obtained by molecular docking simulation.     

Isocyanide terpene metabolites of Phyllidiella pustulosa, a nudibranch from the South China Sea

A series of isocyanides, compounds 4-11, including diterpenes never before found in Phyllidiid nudibranchs, have been isolated from a Chinese population of the nudibranch Phyllidiella pustulosa. Three new sesquiterpenes (8, 10, and 11), with eudesmane, guaiane, and bisabolane skeletons, respectively, have been characterized by spectral methods and chemical comparison with known related molecules. The absolute stereochemistry of the major metabolite, the isocyanide 8, an enantiomer of the known sponge metabolite stylotelline (12), has also been determined.