Molecular Identification of Cutaneous Leishmaniasis Vectors in Alborz Province, North of Iran.

Cutaneous leishmaniasis (CL) is a vector-borne disease widely distributed in tropical and subtropical areas of North and South America, Europe, Asia, and Africa. Considering the increasing number of CL cases in recent years and the fact that no study has been conducted to identify CL fauna and vectors in Alborz province, this study was carried out to identify sand flies and CL vectors in this region. Sand flies were collected from August to October 2021 from plain and mountainous indoor and outdoor areas of the region using sticky paper traps and were detected morphologically. DNA was extracted from the midguts of female sand flies. In this study, 1157 sand flies were collected and identified. The number of sand flies caught from indoor and outdoor places was 367 (31.72%) and 790 (68.28%), respectively. Overall, six species of flies were of the genus Phlebotomus (Raynal, 1937), including Phlebotomus papatasi (P. papatasi, 695 [60.07%]; Scopoli, 1786), P. kandelakii (13 [1.12%]; Shchurenkova, 1926), P. sergenti (232 [20.05%]; Parrot, 1917), P. major (14 [1.21%]; Annandale, 1910), P. caucasicus (4 [0.35%]; Marzinowsky, 1917), P. alexandri (18 [1.56%]; Alexandri Sinton, 1920), and four were of the genus Sergentomyia (Artemiev, 1978), including Sergentomyia tiberiadis (109 [9.42%]; Adler, Theodor & Lourie, 1930), Sergentomyia baghdadis (53 [4.58%]), Sergentomyia sintoni (14 [1.21%]; Sintoni Pringle, 1933), Sergentomyia clydei (5 [0.43%]). P. papatasi spp. were dominant in indoor and outdoor places, with a prevalence of 695 (60.07%). The Leishmania major (L. major) gene was identified in five samples of P. papatasi spp. This suggests that P. papatasi is the potential vector spp. in the study area. Moreover, L. major was confirmed as the aetiological agent of CL cases in Alborz province. The identification of vectors and parasite spp. is very important for the treatment and operational planning of disease vectors.

Detection of Fasciola Hepatica in Lori Sheep Using Polymerase Chain Reaction and Conventional Diagnostic Methods in Western Iran.

Fascioliasis is an emerging and important food and water-borne disease in human communities which has become one of the most important health challenges in countries, like Iran. It causes weight loss, a decrease in feed conversion ratio as well as milk and meat production, and also reduces fertility in animals the prevalence of fasciolosis is increasing in some regions of the world due to various factors. Different methods have been used for the detection of Fasciola hepatica in animals. This study is the first to detect F. hepatica in Lori sheep using polymerase chain reaction (PCR) and conventional diagnostic methods in Western Iran. During three months, 195 fecal samples were collected from sheep in Lorestan province, Iran, using the stratified random sampling method. The conventional diagnostic methods, including wet mount microscopic examination and concentration assays, as well as the PCR technique targeting the intergenic spacer gene of F. hepatica, were used for the detection of the parasite in sheep. In total, 4 (2.1%) out of 195 examined stool samples were positive for F. hepatica based on the conventional assays. The PCR test was positive for F. hepatica in7 (3.6%) samples of 195 studied specimens. Statistical analyses of the data revealed that there is a significant difference between the results of diagnostic methods for F. hepatica detection (P=0.0421). Finally, the results showed that PCR has more diagnostic sensitivity, compared to conventional diagnostic methods, including the concentration techniques and microscopic examination. Hence, it can be advised to use PCR for the detection of F. hepatica in sheep.

Impact of childhood maltreatment on outcomes of antidepressant medication in chronic and/or recurrent depression.

BACKGROUND: While childhood maltreatment (CMT) is associated with higher rates of chronicity and recurrence in depression, whether CMT results in poorer outcomes with antidepressant medication remains unclear. METHODS: We performed secondary analyses with data from the large, representative, multisite trial Combining Medications to Enhance Depression Outcomes (CO-MED). CO-MED was a randomized, single-blinded, placebo-controlled study with 665 individuals (663 assessed for CMT) with chronic and/or recurrent Major Depressive Disorder (MDD). CMT was determined by a brief self-reported questionnaire assessing the four types of CMT defined by the Centers for Disease Control and Prevention: sexual abuse, emotional abuse, physical abuse, and neglect. Repeated measures and logistic regression analyses were used. RESULTS: Individuals with CMT did not have a differential improvement of depressive symptoms when compared to those without CMT (adjusted p=.203 for continuous analysis; adjusted p=.320 for remission rates). Neither type of antidepressant medication (adjusted p=.302) nor the age at which CMT occurred (adjusted p=.509) affected depressive symptom outcomes. There was no difference in functional improvement between individuals with and without CMT (adjusted p=.228). A history of CMT was associated with greater antidepressant side effects (p=.009). LIMITATIONS: This study investigated treatment-seeking individuals with chronic and/or recurrent MDD. Intensity and duration of CMT were not assessed. CONCLUSION: In a sample of treatment-seeking outpatients with chronic and/or recurrent MDD, a history of CMT was not associated with differential symptomatic or functional response to pharmacological treatment. However, those with CMT reported greater antidepressant side effect burden.

Childhood maltreatment and impact on clinical features of major depression in adults.

OBJECTIVES: This study examined: 1) the prevalence of childhood maltreatment (CMT) in individuals with chronic and/or recurrent depression, 2) the association between CMT and depressive symptoms, 3) the link between CMT and worse clinical presentation of depression, 4) the effects of accumulation of different types of CMT, and 5) the relationship between the age at CMT and depression. METHODS: We analyzed the baseline data of 663 individuals from the CO-MED study. CMT was determined by a brief self-reported questionnaire assessing sexual abuse, emotional abuse, physical abuse, and neglect. Correlational analyses were conducted. RESULTS: Half of the sample (n = 331) reported CMT. Those with CMT had higher rates of panic/phobic, cognitive and anhedonic symptoms than those without CMT. All individual types of maltreatment were associated with a poorer clinical presentation including: 1) earlier MDD onset; 2) more severe MDD, 3) more suiccidality, 4) worse quality of life, and functioning, and 5) more psychiatric comorbidities. Clinical presentation was worse in participants who reported multiple types of CMT. CONCLUSIONS: In chronic and/or recurrent depression, CMT is common, usually of multiple types and is associated with a worse clinical presentation in MDD. The combination of multiple types of CMT is associated with more impairment.

Assessment of Gill Pathological Responses in Yellowfin Sea Bream (Acanthopagrus Latus) Under Aeromonas Hydrophila Exposure.

Bacterial diseases in cultured fish are considered the main problem with aquaculture system in Iran. The gills are multifunctional organs responsible for respiration, osmoregulation, nitrogenous waste excretion, and acid-base balance. Moreover, they are very sensitive to water contamination. Aeromonas hydrophila (A. hydrophila) is an opportunist pathogen responsible for a wide range of diseases in different species of fish. The gill histological alterations were used to assess the effects of A. hydrophila exposure on yellowfin sea bream, Acanthopagrus latus (A. latus). In this regard, 90 A. latus were exposed to the concentrations of A. hydrophila (103 and 106 CFU/ml) for three weeks. The most histopathological alterations in the gill of the exposed fish included hypertrophy and hyperplasia of the epithelial cells, lamellar fusion, club shaping of gill lamellae, lifting of the epithelium and edema of lamellae with large sub-epithelial space, blood congestion, and hypertrophy and hyperplasia of the mucosal cells. The histopathological alterations were observed in the gill of fish exposed to higher levels of A. hydrophila (106 CFU/ml) consisted of aneurysm and hemorrhage with blood congestion. According to the obtained results of this study, A. hydrophila could cause severe histopathological changes in the gill of A. latus and decrease gas change capability in yellowfin sea bream. Furthermore, the findings of the present study suggested that histopathological changes of the gill provide helpful information about the environmental conditions and as particular biomarkers may help the evaluation of fish general health.

A Unique Case of Eosinophilic Pancreatitis and Anencephaly in the Fetus of a Type I Diabetic Mother.

Pancreatic infiltration with eosinophils is an uncommon finding with numerous etiologies. While two rare cases of eosinophilic pancreatitis in infants born to Type I diabetic mothers have been reported once in the English literature and once in the French literature, we present the additional finding of anencephaly in a 34 week old fetus. Although the pancreas was grossly unremarkable, histological inspection demonstrated an eosinophilic infiltrate in the fibrous septae and islets of Langerhans along with hypertrophy and hyperplasia of the pancreatic islets.

Evaluation of prophylactic and therapeutic effects of silymarin and N-acetylcysteine in acetaminophen-induced hepatotoxicity in cats.

Cats most commonly receive toxic amounts of acetaminophen (APAP) because owners medicate them without consulting a veterinarian. The aim of this study was to compare the hepatoprotective action of silymarin and N-acetylcysteine (NAC) against APAP poisoning. Twenty healthy cats were randomly allotted to five equal groups. Animals in group A were given APAP (single dose 150 mg/kg, p.o.); groups B and C consisted of cats that received NAC (100 mg/kg, p.o.) or silymarin (30 mg/kg, p.o.) concurrent with APAP administration respectively; groups D and E were treated like groups B and C, respectively, but 4 h after APAP administration. The serum concentrations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), methemoglobin, and total and direct bilirubin were measured before APAP administration and 4, 24, and 72 h later. A single oral administration of APAP significantly elevated serum concentrations of ALT, AST, ALP, LDH, methemoglobin, and total and direct bilirubin. In both the groups receiving APAP plus NAC or silymarin, levels of serum enzyme activities, methemoglobin, and total and direct bilirubin remained within the normal values. It was concluded that silymarin as well as NAC can protect liver tissue against oxidative stress in cats with an APAP intoxication.

Effect of transition metal ions (cobalt and nickel chlorides) on intestinal iron absorption.

BACKGROUND: Haem biosynthesis may regulate intestinal iron absorption through changes in cellular levels of delta-aminolaevulinic acid (ALA), haem and perhaps other intermediates. CoCl2 and NiCl2 are activators of haem oxygenase, the rate-limiting enzyme in haem catabolism. Co2+ and Ni2+ may also regulate and increase iron absorption through a mechanism that simulates hypoxic conditions in the tissues. DESIGN: We assayed intestinal iron absorption in mice dosed with CoCl2 or NiCl2. The effects of these metal ions on splenic and hepatic levels of ALA synthase and dehydratase as well as urinary levels of ALA and phosphobilinogen were also assayed. RESULTS: While Co2+ enhanced iron absorption when administered to mice at doses of 65, 125 and 250 micromoles kg(-1) body weight, Ni2+ was effective only at the highest dose. Ni2+ but not Co2+ at the highest dose reduced urinary ALA in the treated mice. Both metals ions increased splenic expression of haem oxygenase 1 and iron regulated protein 1, proteins involved, respectively, in haem degradation and iron efflux. Co2+ induced erythropoietin expression. CONCLUSIONS: The data suggest that while the effect of Ni2+ on iron absorption could be explained by effects on ALA, the effect of Co2+ may not be explained simply by changes in haem metabolism; therefore, effects mediated by alterations of specific haemoproteins by mechanisms that simulate tissue hypoxia could be important.

An iron-regulated ferric reductase associated with the absorption of dietary iron.

The ability of intestinal mucosa to absorb dietary ferric iron is attributed to the presence of a brush-border membrane reductase activity that displays adaptive responses to iron status. We have isolated a complementary DNA, Dcytb (for duodenal cytochrome b), which encoded a putative plasma membrane di-heme protein in mouse duodenal mucosa. Dcytb shared between 45 and 50% similarity to the cytochrome b561 family of plasma membrane reductases, was highly expressed in the brush-border membrane of duodenal enterocytes, and induced ferric reductase activity when expressed in Xenopus oocytes and cultured cells. Duodenal expression levels of Dcytb messenger RNA and protein were regulated by changes in physiological modulators of iron absorption. Thus, Dcytb provides an important element in the iron absorption pathway.

Congenital cleft-foot deformity treatment.

A retrospective review of congenital cleft foot was done on 16 patients with 32 involved feet. The average age at the time of surgery was 4 years (range, 5 months to 13 years). The average follow-up after surgery was 7.8 years, with a range of 2-45 years. A simple classification based on severity of deficiency was developed. Twenty-three of the 24 procedures performed gave a satisfactory result. Six of the nine untreated feet were satisfactory. Based on our classification, the following treatment is recommended: type I, central partial forefoot cleft was treated by a soft-tissue syndactylism and a partial hallux valgus correction, if needed. Type II, for a complete forefoot cleft to the tarsus, soft-tissue syndactylism with first-ray osteotomy if necessary before age 5 years is recommended. First-ray amputation is advised after age 5 years. Type III: Complete absence of first through fourth ray did not need forefoot surgery.

Endogenous neuropeptide Y mediates vasoconstriction during endotoxic and hemorrhagic shock.

Neuropeptide Y (1-36), NPY, is a sympathetic vasoconstrictor whose activities in blood vessels is determined by the presence of vasoconstrictive Y1 receptors and the enzyme dipeptidyl peptidase IV (DPPIV), which converts NPY to non-vasoconstrictive peptides. While the role of the NPY system has been established during cold water stress, its role in hypotensive conditions has not; yet, exogenous NPY improves hemodynamics and survival in rats with endotoxic shock. We used a new selective non-peptidergic Y1 receptor antagonist, BIBP-3226, to determine the role of the endogenous NPY/Y1 system in endotoxic shock (induced by i.v. injection of 10 mg/kg of Escherichia coli lipopolysaccharide 0127:B8, LPS) and hemorrhagic shock (bleeding of 15 ml/kg over 1.5 min). Conscious rats received a bolus of BIBP-3226 or the vehicle 5 min before endotoxin challenge or induction of hemorrhage, followed by continuous infusion. Mean arterial pressure (MAP) at 5 min after LPS administration dropped in the control group by 15%, compared to 36% in the BIBP-3226-treated group (p < 0.01). Similarly, the hemorrhage-induced drop in MAP in the control group was 32% at 5 min, compared to 53% in the BIBP-treated rats (p < 0.01). Plasma NPY levels were unchanged in the endotoxic shock group, but were significantly elevated in the hemorrhagic shock group. BIBP-3226 pretreatment abrogated the increased plasma NPY levels after hemorrhagic shock. Endogenous NPY contributes to blood pressure recovery during endotoxic and hemorrhagic shock.

The flexor pollicis longus and its relation to the anterior and posterior interosseous nerves.

Sixty paired cadaver upper extremities were dissected to study the anatomy of the flexor pollicis longus in the forearm and its relation to the median and anterior interosseous nerves. An accessory head was noted in 33 (55%) of 60 specimens. The accessory head was noted to pass anterior to the anterior interosseous nerve in all specimens. The accessory head was noted to pass posterior to the median nerve in 57 specimens, and anterior to the nerve in three. Tendon or muscle anomalies were noted in eight specimens (13%), seven of which involved an anomalous attachment between the FPL and the flexor digitorum profundus of the index.

Malignant melanoma in a child with oculocutaneous albinism.

Malignant melanoma is extremely rare in patients with albinism. To date, in the English language literature, there have been only sixteen documented cases of malignant melanoma in albino patients. These cases include thirteen cutaneous, one oral, one ocular, and one anal; only one of these was in a child. Here, we present the case of the youngest known albino patient to have cutaneous malignant melanoma.

Chemical synthesis and surface activity of lung surfactant phospholipid analogs. II. Racemic N-substituted diether phosphonolipids.

A series of racemic 16:0 disaturated N-substituted diether phosphonolipid analogs of glycerophospholipids have been synthesized and purified. Isosteric methylene substitution at three of the four ester sites (carboxyl, phosphate) of conventional glycerophospholipids enhanced the hydrophobicity of analog compounds compared with dipalmitoyl phosphatidylcholine (DPPC), the major glycerophospholipid component of lung surfactant. Further substitutions at the nitrogen headgroup also contributed to hydrophobicity/hydrophilicity characteristics, as well as allowing graded variations in headgroup size among the members of the diether phosphonolipid analog series. Interfacial property studies showed that these compounds had significant differences in surface activity characteristics compared with DPPC, including increased adsorption and respreading facility, plus an enhanced ability to generate low surface tension (less than 1 to 4 mN/m) on an oscillating bubble apparatus at 37 degrees C. In addition, pressure-volume mechanical studies in surfactant-deficient excised rat lungs showed that the diether phosphonate analog of DPPC could partially restore pressure-volume characteristics toward normal, both as a pure component and in binary mixtures with palmitoyl-oleoyl phosphatidylglycerol. These findings suggest that selected analog compounds, synthesized with relatively small structural modifications from biologic glycerophospholipids, may have eventual applications as components of synthetic exogenous lung surfactants. Of more immediate importance, analog molecules with defined structural variations are convenient molecular probes for developing structure-surface activity correlates for phospholipid-like surfactants and for investigating the specificity of interactions between glycerophospholipids and other compounds such as proteins.

Chemical synthesis and surface activity of lung surfactant phospholipid analogs. III. Chiral N-substituted ether-amide phosphonolipids.

A homologous series of chiral (R) ether-amide phosphonolipid analogs of naturally occurring (R) glycerophospholipids were synthesized and characterized for their interfacial behaviors. The phosphonolipids possess isoteric ether, amide, and phosphonate functions at positions corresponding to the sn-1, sn-2, and sn-3 ester functions, respectively, of naturally occurring glycerophospholipids. All compounds were synthesized with disaturated C16:0 alkyl/acyl moieties to give structural analogy with dipalmitoyl phosphatidylcholine (DPPC), the major glycerophospholipid component of lung surfactant. Further substitutions at the headgroup nitrogen were also used to generate differences in headgroup size and polarity in the synthetic compounds. The surface activity of the ether-amide phospholipids was investigated in terms of adsorption to the air-water interface, together with studies of dynamic respreading after monolayer collapse and surface tension lowering in dynamically compressed spread films and dispersions. Results showed that several ether-amide phosphonolipids had more rapid adsorption and improved dynamic respreading behavior compared to DPPC, plus the ability to lower surface tension into the range of less than 1 to 4 mN/m in spread films and in dispersions under dynamic conditions. In combination with a series of diether phosphonolipids synthetized in a companion study [1], these ether-amide compounds are useful in the development of molecular structure-surface activity correlates for lung surfactant-related materials, and should assist in investigating the specificity of interactions between phospholipids and other pulmonary biological molecules.

Preparative-scale high-performance liquid chromatographic separation and purification of 3'-azido-3'-deoxythymidine-5'-phosphate.

Crude 3'-azido-3'-deoxythymidine-5'-phosphate (AZT-P), obtained from direct phosphorylation of 3'-azido-3'-deoxythymidine (azidothymidine, AZT), was separated and purified by isocratic preparative high-performance liquid chromatography. The components in a 2.5-g load of crude AZT-P, obtained from work-up of the phosphorylation reaction, were separated in 50 min to give 1.8 g of 99.5% pure AZT-P. AZT-P was analyzed by high-performance liquid chromatography and by high-resolution nuclear magnetic resonance (1H, 13C, 31P) spectroscopy. The practical and rapid preparative chromatographic method is being applied to the purification of AZT-P and other antiretroviral dideoxynucleotides, used as intermediates in the synthesis of target-directed experimental drugs for the treatment of AIDS.

Anticonvulsant activities of phenyl-substituted bicyclic 2,4-oxazolidinediones and monocyclic models. Comparison with binding to the neuronal voltage-dependent sodium channel.

8,9-Dioxo-6-phenyl-1-aza-7-oxabicyclo[4.2.1]nonane (1) and 9,10-dioxo-7-phenyl-1-aza-8-oxabicyclo[5.2.1]decane (2), examples of anti-Bredt bicyclic 2,4-oxazolidinediones, were investigated as anticonvulsants in mice. Compound 2 was the more potent (anti-MES ED50 = 66 mg/kg), and its in vivo anti-MES effect was consistent with its in vitro potency of binding to the voltage-sensitive sodium channel (IC50 = 160 microM for the inhibition of binding of [3H]BTX-B), suggesting that 2 may be a new class I anticonvulsant. Several partial structures of 2, either monocyclic lactams or monocyclic 2,4-oxazolidinediones, were also evaluated in these assays, but no correlation was observed between sodium channel binding and anti-MES effects. A significant finding was that monocyclic 5-alkyl-5-phenyl-2,4-oxazolidinediones provided relatively potent, nontoxic, broad-spectrum anticonvulsants.