Trajectory of criterion symptoms of major depression under newly started antidepressant treatment: sleep disturbances and anergia linger on while suicidal ideas and psychomotor symptoms disappear early.

OBJECTIVE: In modern psychiatry, depression is diagnosed with the diagnostic criteria; however, the trajectory of each of the criterion symptoms is unknown. This study aims to examine this. METHODS: We made repeated assessments of the nine diagnostic criterion symptoms with the Patient Health Questionnaire-9 (PHQ-9) among 2011 participants of a 25-week pragmatic randomised controlled trial of sertraline and/or mirtazapine for hitherto untreated major depressive episodes. The changes from baseline were estimated with the mixed-effects model with repeated measures. The time to disappearance of each symptom was modeled using the Kaplan-Meier survival analysis. RESULTS: The total score on PHQ-9 was 18.5 (SD = 3.9, n = 2011) at baseline, which decreased to 15.3 (5.2, n = 2011) at week 1, to 11.5 (5.9, n = 1953) at week 3, to 7.8 (6.0, n = 1927) at week 9, and to 6.0 (5.9, n = 1910) at week 25. Suicidal ideas, psychomotor symptoms decreased rapidly, while anergia and sleep disturbance also decreased but only slowly. The survival analyses confirmed the primary analyses. CONCLUSIONS: Upon initiation of antidepressant treatment, patients with newly treated major depressive episodes can expect their suicidal ideas and psychomotor symptoms to disappear first but sleep disturbances and anergia to linger on.

Quantitative analysis of mousy off-flavour compound 2-acetyl tetrahydropyridine in wine using liquid chromatography tandem mass spectrometry interfaced with atmospheric chemical ionisation.

2-Acetyltetrahydropyridine (ACTPY), tautomers of 2-acetyl-1,4,5,6-tetrahydropyridine and 2-acetyl-3,4,5,6-tetrahydropyridine, is reported as one of the major compounds responsible for mousy off-flavour wine. A simple and rapid method for the quantitation of ACTPY in wine using HPLC-APCI-MS/MS was developed. Only filtration and basification were required for sample preparation prior to analysis. The analytical run time was approximately 17 min for one sample. Precision and accuracy tests confirmed that the method was highly reliable and robust. Limits of quantitation (LOQ) for red and white wines were estimated to be 0.23 µg L-1, which was sufficiently sensitive to allow the quantitation of ACTPY at its odour threshold level in water. The method can be implemented for routine objective screening of wines for mousy off-flavour, to determine sensory threshold levels in wine and to aid further research aiming to reduce the occurrence of this fault in wine.

Enthusiasm for homework and improvement of psychological distress in subthreshold depression during behavior therapy: secondary analysis of data from a randomized controlled trial.

BACKGROUND: Cognitive behavioral therapy (CBT) usually involves homework, the completion of which is a known predictor of a positive outcome. The aim of the present study was to examine the session-by-session relationships between enthusiasm to complete the homework and the improvement of psychological distress in depressed people through the course of therapy. METHODS: Working people with subthreshold depression were recruited to participate in the telephone CBT (tCBT) program with demonstrated effectiveness. Their enthusiasm for homework was enhanced with motivational interviewing techniques and was measured by asking two questions: "How strongly do you feel you want to do this homework?" and "How confident do you feel you can actually accomplish this homework?" at the end of each session. The outcome was the K6 score, which was administered at the start of each session. The K6 is an index of psychological distress including depression and anxiety. We used structural equation modeling (SEM) to elucidate the relationships between enthusiasm and the K6 scores from session to session. RESULTS: The best fitting model suggested that, throughout the course of behavior therapy (BT), enthusiasm to complete the homework was negatively correlated with the K6 scores for the subsequent session, while the K6 score measured at the beginning of the session did not influence the enthusiasm to complete the homeworks assigned for that session. CONCLUSIONS: Empirical data now support the practitioners of BT when they try to enhance their patient's enthusiasm for homework regardless of the participant's distress, which then would lead to a reduction in distress in the subsequent week. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT00885014 . April 20, 2009.

Protocol registration and selective outcome reporting in recent psychiatry trials: new antidepressants and cognitive behavioural therapies.

OBJECTIVE: The selective reporting of favorable outcomes has a serious influence on our evidence base. However, this problem has not yet been systematically investigated in the field of psychiatry. Our study aimed to evaluate registration and outcome reporting in randomized controlled trials (RCTs) of standard treatments for depression: cognitive behavioural therapy (CBT) or new-generation antidepressants (ADs). METHOD: We searched for reports of RCTs examining the efficacy of CBT or AD for depression that were published between 2011 and 2013. We then compared their primary outcomes in the trial registries and those in publications. RESULTS: We identified 170 trials. Among them, 92 trials (54.1%) were registered, 43 trials (25.3%) were properly registered, and only 32 (18.8%) trials were both properly registered and reported (the primary outcomes as recorded in the registries were reported in publications). There was no statistically significant difference in the proportions of properly registered and reported trials for CBT or AD (relative risk: 0.51, 95% CI: 0.25-1.03). High impact factor journals, commercial funding, publication of protocol, and relatively large sample size were significant predictors of proper registration and reporting. CONCLUSION: The prevalence of proper registration and reporting is still very low in depression trials.

Analysis of phthalates in wine using liquid chromatography tandem mass spectrometry combined with a hold-back column: Chromatographic strategy to avoid the influence of pre-existing phthalate contamination in a liquid chromatography system.

This paper describes the development and application of a novel method for the analysis of phthalates in wine using HPLC-MS/MS combined with a hold-back column. Phthalates are ubiquitous contaminants in the environment and can be widely found in laboratory materials and equipment. A HPLC system is no exception and can be the source of contamination affecting the accuracy and precision of analytical results. The new method successfully separates phthalates from the different sources, a wine sample and HPLC system by a simple technique using an additional HPLC column (a hold-back column) placed upstream of the injection valve. The hold-back column effectively retains the HPLC-derived contaminants during column equilibrium time and delays their elution times from an analytical column. Consequently, a phthalate from a wine sample can be baseline separated as it elutes sufficiently earlier than the same phthalate from the HPLC system. HPLC-MS/MS analysis combined with the hold-back column demonstrated virtually no influence of the HPLC contaminants on the quantification of phthalates present in wine. Together with a simple and rapid sample preparation and the use of labeled internal standards, the method was confirmed to be robust and reliable to determine concentrations of phthalates in wine. Quantification limits were within the range of 1.6-9.8µgL-1 for dimethyl, diethyl, dibutyl, benzylbutyl, bis(2-ethylhexyl) and dioctyl phthalates, and 7.5-26.6µgL-1 for multiple isomeric phthalates, di-iso-nonyl and di-iso-dodecyl phthalates.

Identification of a beta-D-glucopyranoside precursor to guaiacol in grape juice following grapevine exposure to smoke.

The presence of the beta-D-glucopyranoside of guaiacol (glucoside) in juice of grapes following grapevine exposure to smoke was investigated. The glucoside was synthesized as a reference compound and an HPLC-MS/MS method was developed for its detection in juice. The glucoside was found in the juice extracts of grapes exposed to bushfire smoke, as well as grapes experimentally exposed to smoke. Compared to the control (unsmoked) juice sample, the experimentally smoked juice contained a significant amount of the glucoside, indicating glucosylation of guaiacol occurred following grapevine smoke exposure. The reference compound, and the glucoside found in the smoked juice samples were less susceptible to acid treatment but virtually disappeared after enzyme treatment with beta-glucosidase. The susceptibility of the glucoside to enzyme hydrolysis could be one reason for the release of guaiacol from smoke affected grapes during fermentation.

Ocular manifestations in patients with microscopic polyangiitis.

PURPOSE: To describe ocular manifestations in patients with microscopic polyangiitis. METHODS: Two patients with microscopic polyangiitis complained of ocular symptoms and underwent ophthalmologic examinations. RESULTS: An 83-year-old woman (Case 1) was diagnosed with microscopic polyangiitis, according to the general clinical findings and the presence of perinuclear pattern of antineutrophil cytoplasmic antibodies (P-ANCA). She had hypopyon iridocyclitis in the right eye and retinal cotton-wool spots in the left eye. The patient was treated with oral prednisolone and subconjunctival betamethasone. The hypopyon iridocyclitis and retinal cotton-wool spots responded. A 79-year-old man (Case 2) had bilateral scleritis. The diagnosis of microscopic polyangiitis was made based on general clinical findings and the presence of P-ANCA. Scleritis was reduced after corticosteroid treatment. CONCLUSIONS: Ophthalmologists should be aware that hypopyon iridocyclitis, cotton-wool spot, and scleritis could occur in patients with microscopic polyangiitis.

Cyanogenic glucosides in grapevine: polymorphism, identification and developmental patterns.

Twelve grapevine (Vitis vinifera L.) cultivars were surveyed for 'cyanide potential' (i.e. the total cyanide measured in beta-glucosidase-treated crude, boiled tissue extract) in mature leaves. Two related cultivars (Carignan and Ruby Cabernet) had mean cyanide potential (equivalent to 110 mgHCNkg-1fr.wt) ca. 25-fold greater than that of the other 10 cultivars, and so the trait is polymorphic in the species. In boiled leaf extracts of Carignan and Ruby Cabernet, free cyanide constituted a negligible fraction of the total cyanide potential because beta-glucosidase treatment was required to liberate the major cyanide fraction - which is therefore bound in glucosylated cyanogenic compound(s) (or cyanogenic glucosides). In addition, cyanide was liberated from ground leaf tissue of Ruby Cabernet but not Sultana (a cultivar with low cyanide potential). Hence, the high cyanide potential in Ruby Cabernet leaves is coupled with endogenous beta-glucosidase(s) activity and this cultivar may be considered 'cyanogenic'. A method was developed to detect and identify cyanogenic glucosides using liquid chromatography combined with tandem mass spectrometry (LC-MS/MS). Two putative cyanogenic glucosides were found in extracts from leaves of Carignan and Ruby Cabernet and were identified as the epimers prunasin and sambunigrin. Cyanide potential measured at three times over the growing season in young and mature leaves, petioles, tendrils, flowers, berries, seeds and roots of Ruby Cabernet was substantially higher in the leaves compared with all other tissues. This characterisation of cyanogenic glucoside accumulation in grapevine provides a basis for gauging the involvement of the trait in interactions of the species with its pests and pathogens.

Bilateral congenital macular coloboma in a boy with Down syndrome.

PURPOSE: To describe macular coloboma in Down syndrome. METHODS: A 12-year-old boy with Down syndrome underwent ophthalmologic examination. RESULTS: The patient had a circumscribed, round defect about 1 disc diameter, with bared sclera at the base and pigment clump at the macula in both fundi. His poor visual acuity was unchanged since childhood. The results of serum IgG and IgM titers for Toxoplasma gondii were negative. CONCLUSIONS: Congenital macular coloboma associated with Down syndrome, as demonstrated in our patient, may not have occurred by chance.

Isolation and structures of oligomeric wine pigments by bisulfite-mediated ion-exchange chromatography.

Methods have been developed that are based on cation exchange chromatography in the absence and presence of excess bisulfite for the isolation of wine pigments from Australian red wine and grape marc extract. The pigments were identified using HPLC and electrospray ionization mass spectrometry. The mass spectral data indicate that these pigments are C4-substituted anthocyanins with a tetracyclic structure. The pigments form a series of closely related oligomeric pigments which include those previously described in the literature, such as pigment A and vitisin A, as well as some newly identified pigments.

Composition of grape skin proanthocyanidins at different stages of berry development.

The composition of grape (Vitis vinifera L. cv. Shiraz) skin proanthocyanidins has been determined at different stages of berry development. Beginning approximately 3 weeks after fruit set and concluding at commercial ripeness, the composition of isolated skin proanthocyanidins was determined using the following analytical techniques: elemental analysis, UV-Vis absorption spectroscopy, reversed-phase HPLC after acid-catalysis in the presence of excess phloroglucinol, gel permeation chromatography, electrospray ionization mass spectrometry (ESI-MS), and (13)C NMR. On the basis of these analyses, berry development was correlated with an increase in proanthocyanidin mean degree of polymerization, an increase in the proportion of (-)-epigallocatechin extension subunits, and increases in the level of anthocyanins associated with the proanthocyanidin fraction. Additionally, data acquired from ESI-MS of the isolates following acid-catalysis in the presence of excess phloroglucinol is consistent with pectin-bound proanthocyanidins.

Ocular changes after intravitreal injection of methanol, formaldehyde, or formate in rabbits.

We evaluated the effects of intravitreal injection of methanol, formaldehyde, or formate on rabbit eyes. One hundred microl of 1% methanol, 1% or 0.1% formaldehyde, or 1% formate was injected in the vitreous cavity of the right eyes of rabbits. The eyes were examined by biomicroscopy and ophthalmoscopy weekly. One month after injection, the eyes were enucleated and examined histologically. One week after treatment the animals that received 0.1% formaldehyde showed retinal vessel dilation, and the rabbits that received 1% formaldehyde showed mild posterior subcapsular cataract and retinal vessel dilation and haemorrhages. One month after treatment, the animals that received 0.1% or 1% formaldehyde developed mild posterior subcapsular cataract and retinal lesions. Animals that received 1% methanol or 1% formate showed nearly normal optical media and fundi. Histologically disorganized retina and optic nerve were seen in eyes that received 0.1% or 1% formaldehyde. Eyes that received 1% methanol or 1% formate appeared histologically normal. Our findings indicate that intravitreal injection of formaldehyde causes retinal and optic nerve damage, while methanol and formate are not or less toxic to ocular tissues.

Peripherin/RDS gene mutation (Pro210Leu) and polymorphisms in Japanese patients with retinal dystrophies.

PURPOSE: To determine the frequency of peripherin/RDS (retinal degeneration slow) gene mutations in Japanese patients with retinal dystrophies. METHODS: We analyzed the peripherin/RDS gene in 54 unrelated Japanese patients with retinal dystrophies. Genomic DNA was amplified by polymerase chain reaction (PCR) and the PCR products were sequenced. We also examined 100 healthy subjects, seeking mutations or variations of the peripherin/RDS gene. RESULTS: Of the 54 Japanese patients, one with retinitis pigmentosa had a heterozygous C to T change at the second nucleotide at codon 210 of exon 2 (CCT to CTT/Pro210Leu) of the peripherin/RDS gene. None of the 100 individuals with normal fundi had the Pro210Leu mutation of the peripherin/RDS gene. Three variants of the peripherin/RDS gene (GTC to GTT/Val106Val, Glu304Gln, and Gly338Asp) were also found. The first variation (GTC to GTT/Val106Val) was silent. Two concurrent missense variations (Glu304Gln and Gly338Asp) were seen in 25.9% of the affected patients and in 29% of the healthy individuals. CONCLUSION: A novel mutation (Pro210Leu) of the peripherin/RDS gene has been found in one Japanese patient with retinitis pigmentosa. The alterations of Val106Val, Glu304Gln, and Gly338Asp may be polymorphic variants in the Japanese population.

Effects of scutellariae radix extract and its components (baicalein, baicalin, and wogonin) on the experimental elevation of aqueous flare in pigmented rabbits.

PURPOSE: To evaluate the possible inhibitory effects of hot water extract of Scutellariae radix and its major components (baicalein, baicalin, and wogonin) on experimental elevation of aqueous flare in pigmented rabbits. METHODS: To produce aqueous flare elevation in rabbits, prostaglandin E(2) (PGE(2)), 25 microg/mL, was applied to the cornea with the use of a glass cylinder, or lipopolysaccharides (LPS), 0.5 microg/kg, were injected into an ear vein. Animals were pretreated by the oral administration of 150 g/day of food containing 0.02%, 0.07%, or 0.2% (w/w) extract of Scutellariae radix for 5 days, or by intravenous injection of baicalein, baicalin, or wogonin, 60 microg/kg or 600 microg/kg, 30 minutes before experimental uveitis was induced. Aqueous flare was measured with a laser flare-cell meter. Aqueous flare intensity was expressed as the area under the curve (AUC) in arbitrary units. RESULTS: The AUC of PGE(2)- and LPS-induced aqueous flare elevation was 1,343 and 5,066 arbitrary units, respectively. Pretreatment by oral administration of 0.07% or 0.2% extract of Scutellariae radix did not inhibit PGE(2)-induced aqueous flare elevation (AUC: 1,252 and 1,210, respectively), but it did inhibit LPS-induced aqueous flare elevation (AUC: 2,248 and 1,973, respectively). Pretreatment by intravenous injection of 600 microg/kg of baicalein, baicalin, or wogonin inhibited LPS-induced aqueous flare elevation (AUC: 2,289, 2,163, and 1,509, respectively). Pretreatment with 60 microg/kg of wogonin also inhibited LPS-induced aqueous flare elevation (AUC: 1,980). CONCLUSION: Hot water extract of Scutellariae radix may have an inhibitory effect on experimental anterior uveitis induced by LPS in pigmented rabbits.

Effects of traditional Sino-Japanese herbal medicines on aqueous flare elevation after small-incision cataract surgery.

We evaluated prospectively the effects of traditional Sino-Japanese herbal medicines on elevation of aqueous flare. Fifty-four patients with age-related cataract undergoing phacoemulsification with intraocular lens implantation were studied. In the control group, 20 patients received no herbal medicine. In the treated groups, 14 patients were given Orengedoku- to (Huanglian-Jie-Du-Tang in Chinese) granules (7.5 g daily), 10 patients were given Kakkon-to (Ge-Gen-Tang in Chinese) granules (7.5 g daily), and 10 patients were given Sairei-to (Cai-Ling-Tang in Chinese) granules (9.0 g daily), for 3 days before surgery, the day of surgery, and for 7 days after surgery. Aqueous flare was measured before and after surgery. The differences in preoperative flare intensities among the four groups were not significant. In the control group, the flare was 29.4 photon counts/msec on day 1, and then gradually decreased. The flare intensities on days 1, 3, and 5 in the Orengedoku-to and Kakkon-to groups were significantly lower than in the control group. The flare intensities in the Sairei-to group were the same as those of the controls. Oral administration of Orengedoku-to and Kakkon-to decreased aqueous flare elevation after small-incision cataract surgery. Sairei-to had no effect on the elevation.

Use of electrospray mass spectrometry for mass determination of grape (Vitis vinifera) juice pathogenesis-related proteins: a potential tool for varietal differentiation.

Methods based on liquid chromatography-mass spectrometry (LC-MS) and protein trap mass spectrometry (trap-MS) were developed to determine the complement of pathogenesis-related (PR) proteins in grape juice. Trap-MS was superior to LC-MS in terms of simplicity, rapidity, and sensitivity. Proteins with a wide range of masses (13--33 kDa) were found in the juices of 19 different varieties of grape (Vitis vinifera) and were identified as mostly PR-5 type (thaumatin-like) and PR-3 type (chitinases) proteins. Although the PR proteins in juices of grapes are highly conserved, small consistent differences in molecular masses were noted when otherwise identical proteins were compared from different varieties. These differences persisted through different harvest years and in fruits grown in different Australian locations. With the definition of four different masses for PR-5 proteins (range = 21,239--21,272 Da) and nine different masses of PR-3 proteins (range = 25,330--25,631 Da) and using statistical analysis, the methods developed could be used for varietal differentiation of grapes grown in several South Australian locations on the basis of the PR protein composition of the juice. It remains to be seen whether this technology can be extended to grapes grown worldwide and to wine and other fruit-derived products to assist with label integrity to the benefit of consumers.

Effects of Orengedoku-to and Senkanmeimoku-to, traditional herbal medicines, on the experimental elevation of aqueous flare in pigmented rabbits.

We investigated the effects of Orengedoku-to (Huanglian-Jie-Du-Tang in Chinese) and Senkanmeimoku-to (Xygan-Ming-Mu-Tang in Chinese), traditional herbal medicines, on experimantal elevation of aqueous flare in pigmented rabbits. To produce the elevation of aqueous flare in rabbits, prostaglandin E2 (PGE2) was applied to the cornea with use of a glass cylinder, or lipopolysaccharides (LPS) were injected into the ear vein. Animals were pretreated by the oral administration of 150 g/day of food containing 0.7%, 0.2% or 0.07% (w/w) Orengedoku-to, or 2%, 0.6% or 0.2% (w/w) Senkanmeimoku-to for 5 days. Aqueous flare was measured with a laser flare-cell meter. Pretreatment with 0.7% or 0.2% Orengedoku-to and 2% Senkanmeimoku-to did suppress significantly (P < 0.05) elevation of aqueous flare induced by PGE2. Pretreatment with 0.7% or 0.2% Orengedoku-to and 2% or 0.6% Senkanmeimoku-to significantly suppressed (P < 0.001) elevation of aqueous flare induced by LPS. It is possible that Orengedoku-to and Senkanmeimoku-to may migrate some forms of uveitis.

Quantitative analysis of polymeric procyanidins (Tannins) from grape (Vitis vinifera) seeds by reverse phase high-performance liquid chromatography.

A reverse phase C(18) HPLC method with potential for high automated throughput has been developed for the quantitative analysis of polymeric procyanidins (tannins) in grape seed extracts. Chromatography gave rise to 13 distinct UV-absorbing peaks with good baseline separation. The UV-absorbing peak eluting last is distinct and therefore easily quantified. Biochemical analyses including ultrafiltration, protein precipitation, and Sephadex LH20 chromatography combined with electrospray mass spectrometric analyses establish that this peak predominantly contains polymeric procyanidins. The polymers, which appear to be galloylated to various degrees and seem to fragment in a characteristic manner during electrospray mass spectrometry, are well separated from catechins and procyanidin oligomers of up to 4 units. The recovery of polymeric grape seed tannins with this HPLC method was 86%, which is similar to the 89% recovery achieved with commercial quebracho tannins. The concentration of tannins in seeds from ripe Vitis vinifera cv. Shiraz grapes ranged from 1360 to 2830 mg/kg of berries.

Unilateral symptomatic elevation of intraocular pressure and prevention using a hyperosmotic agent during hemodialysis.

BACKGROUND: We report on a patient with unilateral elevation of intraocular pressure during hemodialysis. CASE: A 60-year-old man with unilateral exfoliative material complained of severe pain in the right eye during hemodialysis. OBSERVATIONS: The intraocular pressure (IOP) in the patient's right eye was 56 mm Hg, and increased repeatedly during hemodialysis. The IOP in his left eye remained within a normal range. Trabeculectomy failed to reduce the elevation of IOP in the right eye. Changes in plasma osmotic pressure during hemodialysis were marked when the IOP was elevated. The administration of a hyperosmotic agent prevented the elevation of IOP during hemodialysis. CONCLUSIONS: Physicians should be aware that elevation of IOP in patients with eyes with exfoliative material may occur during hemodialysis even after trabeculectomy. This can be prevented by administering a hyperosmotic agent during hemodialysis.

Effect of topical betaxolol on acute rise of aqueous flare induced by prostaglandin E(2) in pigmented rabbits.

PURPOSE: To evaluate the effects of topical betaxolol on experimental ocular inflammation. METHODS: Transcorneal diffusion of 25 microg/mL (7.09 x 10(-2) mmol/L) of prostaglandin E(2) (PGE(2)), placed in a glass cylinder, was employed to induce aqueous flare elevation in pigmented rabbits. Betaxolol was administered topically before PGE(2) application. Aqueous flare was measured with a laser flare cell meter. RESULTS: Four-, two-, and one-time topical instillations of betaxolol inhibited the PGE(2)-induced aqueous flare elevation by 44% +/- 8%, 32 +/- 7%, and 8 +/- 6%(mean +/- SD), respectively. The inhibition of flare elevation was dependent on the number of betaxolol instillations. CONCLUSION: Topical betaxolol has an inhibitory effect on PGE(2)-induced aqueous flare elevation in rabbit eyes.