Modulating the phototoxicity and selectivity of a porphyrazine towards epidermal tumor cells by coordination with metal ions.

Porphyrazines (Pzs) are porphyrin derivatives that show potential application as photosensitizers for photodynamic therapy (PDT), but are still far less explored in the literature. In this work, we evaluate how the photophysics and phototoxicity of the octakis(trifluoromethylphenyl)porphyrazine (H2Pz) against tumor cells can be modulated by coordination with Mg(II), Zn(II), Cu(II) and Co(II) ions. Fluorescence and singlet oxygen quantum yields for the Pzs were measured in organic solvents and in soy phosphatidylcholine (PC) liposomes suspended in water. While H2Pz and the respective complexes with Cu(II) and Co(II) showed very low efficiency to fluoresce and to produce 1O2, the Mg(II) and Zn(II) complexes showed significantly higher quantum yields in organic solvents. The fluorescence of these two Pzs in the liposomes was sensitive to the fluidity of the membrane, showing potential use as viscosity markers. The cytotoxicity of the compounds was tested in HaCaT (normal) and A431 (tumor) cells using soy PC liposomes as drug carriers. Despite the low 1O2 quantum yields in water, the Mg(II) and Zn(II) complexes showed IC50 values against A431 cells in the nanomolar range when activated with low doses of red LED light. Their phototoxicity was ca. three times higher for the tumor cells compared to the normal ones, showing promising application as photosensitizers for PDT protocols. Considering that H2Pz and the respective Co(II) and Cu(II) complexes were practically non-phototoxic to the cells, we demonstrate the importance of the central metal ion in the modulation of the photodynamic activity of porphyrazines.

Cytomegalovirus as a possibly overlooked agent of hypertensive anterior uveitis and endotheliitis in immunocompetent patients in Brazil.

Cytomegalovirus (CMV) is a member of the Herpesviridae family, including viruses that are well-known agents of keratitis, anterior uveitis, scleritis and retinitis. CMV is usually associated with ocular diseases in immunosuppressed individuals, with a notable exception of hypertensive anterior uveitis with distinctive clinical features in immunocompetent patients. This syndrome was characterized in the last two decades in Europe and Southeast Asia, and then documented in the rest of world. Definitive diagnosis in these cases is usually made by Polymerase Chain Reaction (PCR) of the anterior chamber fluid. We report three immunocompetent Brazilian adults with history of multiple glaucomatocyclitic crises and presenting with chronic hypertensive anterior uveitis invariably with mild anterior chamber inflammation and characteristic scarce nummular keratic precipitates. CMV DNA was successfully amplified and detected in the aqueous humor of all patients. Corneal endothelial counts were significantly reduced in the involved eyes, with one patient developing bullous keratopathy. All patients were then treated with topical ganciclovir gel and corticosteroids, with subsequent control of the intraocular inflammation. CMV may represent an overlooked / underestimated etiology of hypertensive anterior uveitis that may progressively lead to endothelial dysfunction, culminating in bullous keratopathy. Management of patients is challenging, with the potential use of topical antivirals to decrease the number of relapses, and corticosteroids to control anterior uveitis / endotheliitis and to protect the corneal endothelium.

Impact of polyphenols in phagocyte functions.

Polyphenols are a broad group of substances with potential health benefits found in plant species. Several of these compounds are capable of influencing the activation of intracellular signaling pathways, such as NF-kB, MAPK and JAK-STAT, responsible for the production of various inflammatory mediators such as tumor necrosis factor α (TNF-α) and interleukin 1 beta (IL-1ß) and 12 (IL-12), enzymes involved in the production of reactive species such as inducible nitric oxide synthase (iNOS) and superoxide dehydrogenase (SOD), as well as enzymes involved in the production of eicosanoids, such as cyclooxygenase (COX) and lipoxygenase (LO). There is increased interest in the use of polyphenol-rich foods because of their immunomodulatory effect; however, the mechanisms used during macrophage responses are extremely complex and little is known about the effects of polyphenols on these cells. As such, this review summarizes the current view of polyphenol influences on macrophages.

Characterization of Retinopathy Among Patients With Yellow Fever During 2 Outbreaks in Southeastern Brazil.

IMPORTANCE: Yellow fever still threatens people in endemic areas, and besides conjunctival icterus, little is known about the ocular changes that occur in these patients. OBJECTIVE: To characterize retinal changes in patients with confirmed yellow fever during 2 recent outbreaks of the disease in Minas Gerais, Southeastern Brazil. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional, observational study conducted at a single referral center for infectious diseases in Southeastern Brazil collected data between January 2017 and February 2018 from 94 consecutive patients with suspicion of yellow fever who were eligible for the study. MAIN OUTCOMES AND MEASURES: Patients underwent ophthalmic examination. Clinical findings, laboratory results, and occurrence of retinopathy and death during hospitalization were reported, including age, sex, comorbidities, disease severity, serum aspartate aminotransferase level, total bilirubin level, serum creatinine level, arterial lactate level, international normalized ratio, and platelet count at hospital admission. RESULTS: In total, 64 patients were included who had received a confirmed diagnosis of yellow fever, with a median (interquartile range) age of 47 (38-56) years, and 12 patients (19%) were women. Twenty eyes (16%) of 13 patients (20%) had retinopathy at the same time as yellow fever. The most common fundus changes among the 20 eyes were retinal nerve fiber layer infarcts (11 [55%]), superficial hemorrhages (7 [35%]) and grayish deep lesions (6 [30%]), possibly at the level of the outer retina or choroid. Aspartate aminotransferase levels higher than 3000 U/L (odds ratio [OR], 14.2; 95% CI, 3.5-77.8; P < .001), total bilirubin levels higher than 2.3 mg/dL (OR, 20.0; 95% CI, 4.4-159.7; P < .001), serum creatinine levels higher than 2.0 mg/dL (OR, 8.2; 95% CI, 2.1-36.0; P = .003), arterial lactate levels higher than 17.1/mg/dL (OR, 4.6; 95% CI, 1.1-19.0; P = .03), platelet count lower than 94 × 103/µL (OR, 7.8; 95% CI, 1.8-59.9; P = .004), and classification of disease as severe (OR, 11.7; 95% CI, 2.0-301.0; P = .003) were associated with retinopathy. Arterial hypertension, diabetes, international normalized ratio, and death were not associated with retinopathy. CONCLUSIONS AND RELEVANCE: Retinopathy was present in 20% of patients with yellow fever and appeared to be associated with more severe systemic disease. Retinal nerve fiber layer infarcts and superficial hemorrhages, but not the grayish deep lesions, resembled those associated with other flavivirus (eg, dengue virus) infections. The clinical relevance of these findings may warrant further investigation.

Mercury in breast milk from women in the Federal District, Brazil and dietary risk assessment for breastfed infants.

Mercury is a toxic metal, ubiquitous in nature; it is excreted in breast milk from exposed mothers and may affect infant neuro-development. In this study, 224 breast milk samples provided by eight human milk banks in the Federal District of Brazil were analyzed for total mercury (THg), of which 183 were also analyzed for methyl mercury (MeHg), the most relevant form of this metal for the breastfed infants. Samples were acid digested in a microwave oven and THg determined by atomic fluorescence spectrometry (LOQ of 0.76µg/L). Samples were lyophilized, ethylated and MeHg determined in a MERX automated system (LOQ of 0.10µg/L). Inorganic mercury (IHg) levels were estimated from the THg and MeHg determined in the samples. Most of the samples were collected 1-2 months postpartum, with 38% during the first month. Over 80% of the samples had THg values above the LOQ, reaching a maximum of 8.40µg/L, with a mean of 2.56µg/L. On average, MeHg accounted for 11.8% of THg, with a maximum of 97.4%. Weekly intakes were estimated individually, considering the baby's age and body weight at the time of milk collection. Mean weekly intake for MeHg was 0.16±0.22µg/kg bw, which represented 10% of the PTWI; in only one case, the intake exceeded 100% of the PTWI (1.90µg/kg bw, 119% of PTWI). Mean intake for IHg was 2.1±1.5µg/kg bw, corresponding to 53% PTWI. These results indicate no health concern for the breastfed babies, a conclusion that can be extended to the consumers of breast milk donated to the milk banks, primarily immature and low weight babies.

Intrastromal corneal ring segments implantation in patients with keratoconus: 10-year follow-up.

PURPOSE: To evaluate the long-term safety and efficacy of Ferrara intrastromal corneal ring segments (ICRS) (Ferrara Ring; AJL, Boecillo, Spain) in patients with keratoconus. METHODS: The chart records of 36 eyes of 30 patients with keratoconus implanted with ICRS, operated on between July 1996 and January 2002, were retrospectively reviewed. The following parameters were studied: uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), keratometry (K), and central corneal thickness. The outcomes were evaluated at 5 and 10 years after ICRS implantation. RESULTS: The mean UDVA (logMAR) improved from 1.01 ± 0.28 (20/200 Snellen) to 0.71 ± 0.38 (20/100 Snellen) at 5 years (P < .05) and 0.67 ± 0.25 (20/90 Snellen) at 10 years (P = .735). The mean CDVA (logMAR) improved from 0.45 ± 0.45 (20/55 Snellen) to 0.24 ± 0.19 (20/35 Snellen) at 5 years (P < .05) and 0.29 ± 0.09 (20/38 Snellen) at 10 years (P = .292). The mean maximum K value decreased from 54.99 ± 6.33 to 50.58 ± 5.11 D at 5 years (P < .05) and 50.65 ± 5.17 D at 10 years (P = .854). The mean minimum K value decreased from 48.85 ± 5.70 to 46.90 ± 5.08 D at 5 years (P < .05) and 47.12 ± 4.22 D at 10 years (P = .945). The central corneal thickness decreased from 457.42 ± 58.21 to 421.34 ± 74.12 µm at 5 years (P = .039) and 434.32 ± 77.65 µm at 10 years (P = .427). CONCLUSIONS: Intrastromal corneal ring segments can effectively improve UDVA and CDVA 10 years after implantation in patients with keratoconus.

Clinical outcomes after intrastromal corneal ring segments reoperation in keratoconus patients.

AIM: To evaluate the clinical outcomes after Ferrara intrastromal corneal ring segments (ICRS) reoperation in patients with keratoconus. METHODS: A total of 37 keratoconus eyes implanted with intrastromal corneal ring segments, which had an ICRS exchange, addition, reposition or removal were evaluated. Uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA), keratometry (K), asphericity (Q) and pachymetry at the thinnest point (PTP) of the cornea were evaluated using a corneal tomography (Oculus Pentacam, USA). RESULTS: The mean follow-up time after the reoperation was 30.5±9.7 months. The mean UCVA improved from 20/300 to 20/80 (P=0.005); the mean BCVA improved from 20/160 to 20/50 (P=0.0002), the mean keratometry reduced from 49.33±4.19D to 46.16±3.90D (P=0.0001), the mean pachymetry at the thinnest point increased from 450±42.9µm to 469±40.8µm (P=0.0001). The asphericity increased from -0.84±0.74 to -0.35±0.81 (P=0.15) and the spherical equivalent reduced from -4.64±4.87D to -3.04±3.45D (P=0.137). The changes in the asphericity and spherical equivalent were not statistically significant. CONCLUSION: Ferrara ICRS implantation showed to be a reversible and readjustable surgical procedure for keratoconus treatment. Good outcomes can be obtained even after removal, addition, reposition or exchange of ICRS.

Mercury concentration in breast milk and infant exposure assessment during the first 90 days of lactation in a midwestern region of Brazil.

Breast milk samples collected from 18 nursing mothers between the 15th and 90th day of lactation were digested in nitric acid in a microwave, and total mercury (THg) levels were quantified by atomic fluorescence spectrometry. Participants responded to a 24-h dietary recall questionnaire on the 74th and 76th day of lactation and to a Food Frequency Questionnaire querying the frequency of fish intake over the last 90 days. Usual intake was estimated using the PC-SIDE software package. A meal of fish was offered on the 75th day of lactation. Mothers' individual mean THg levels ranged from <0.76 to 22.7 ng/mL during the period, and the mean level for all samples (n = 142) was 6.47 ±6.04 ng/mL. The multilevel mixed linear model used showed high heterogeneity of the mercury levels among the mothers, and THg levels did not change significantly over the period under study. However, a significant increase in THg levels was observed after the intervention with the fish meal. Exposure increased for most infants on the 90th day of lactation, with intakes exceeding the THg provisional tolerable weekly intake (PTWI) at least once during the period for 77.8 % of samples. Mothers consumed mostly food from the fat and grain groups, and a significant correlation was detected between consumption of food of these groups and breast milk THg levels (p = 0.006 and 0.007). A significant correlation was also found between vegetable consumption and carbohydrate intake and THg levels in the samples (p = 0.015 and 0.045, respectively). No correlation was found between mothers' daily fish consumption frequency and THg levels. Although this study showed that mercury intake by infants during lactation may exceed the toxicologically safe exposure level (PTWI), we nevertheless believe that the benefits of lactation for both the mother and the infant outweigh the eventual risks that this exposure may represent.

Toxic metals (Pb and Cd) and their respective antagonists (Ca and Zn) in infant formulas and milk marketed in Brasilia, Brazil.

In non-ideal scenarios involving partial or non-breastfeeding, cow's milk-based dairy products are mainstream in infant feeding. Therefore, it is important to study the concentrations of potentially neurotoxic contaminants (Pb and Cd) and their respective counteracting elements (Ca and Zn) in infant dairy products. Fifty-five brands of infant formulas and milk sold in Brasilia, Brazil were analyzed. The dairy products came from areas in the central-west (26%), southeast (29%) and south of Brazil (36%) extending as far as Argentina (7%) and the Netherlands (2%). For toxic Pb and Cd, median concentrations in powdered samples were 0.109 mg/kg and 0.033 mg/kg, respectively; in fluid samples median Pb concentration was 0.084 mg/kg, but median Cd concentration was below the limit of detection and overall values were below reference safety levels. However, 62% of these samples presented higher Pb concentration values than those established by FAO/WHO. Although the inverse correlation between Cd and Zn (Spearman r = -0.116; P = 0.590) was not statistically significant, the positive correlation between Ca and Pb was (Spearman r = 0.619; P < 0.0001). Additionally, there was a significant correlation between Pb and Cd. Furthermore, the study also revealed that provision of the essential trace element Zn in infant formulas can provide adequate amounts of the recommended daily requirements. Infant formulas and milk sold for consumption by infants and children can be an efficient tool to monitor neurotoxic metal risk exposure among young children.

Apendicite aguda por Enterobius vermicularis: relato de caso e revisão da literatura / Acute appendicitis and Enterobius vermicularis: case report and review of the literature

O parasitismo pelo Enterobius vermicularis é assintomático na maioria dos pacientes. A sintomatologia, quando presente, caracteriza-se, principalmente, pelo prurido anal, entretanto, podem estar presentes dores abdominais esporádicas sem suspeita da parasitose. A relação entre apendicite aguda e enterobíase é rara e motivo de controvérsia. A presença do parasito no apêndice cecal, segundo alguns autores, pode ser incidental, embora possa ser responsável pelo desenvolvimento de apendicite crônica. Relata-se, neste trabalho, o desenvolvimento de apendicite aguda em um paciente, provocada por Enterobius vermicularis, e revisão da literatura sobre o assunto.

Enterobius vermicularis infection is asymptomatic in the majority of the patients. When symptoms do appear, the most characteristic is the very strong anal itching sensation. Abdominal tenderness may occur sporadically, however, it does not direct for the diagnosis. The relationship between acute appendicitis and enterobiasis is debatable and controversial. Many believe that the presence of the parasite in the appendix is an incidental operative finding, although, enterobiasis has been attributed to cases of chronic appendicitis. We report a case of acute appendicitis provoked by Enterobius vermicularis and review the literature on the topic.

Bis(tetra-phenyl-phospho-nium) bis-[N-(octyl-sulfon-yl)dithio-carbimato(2-)-κS,S']-nickelate(II).

The Ni atom in the title complex, (C(24)H(20)P)(2)[Ni(C(9)H(17)NO(2)S(3))(2)], lies on a twofold axis within a square-planar geometry defined by four S atoms derived from two dithio-carbimate dianions, each forming a four-membered chelate ring. A small distortion, described by a deviation of the Ni(II) atom by 0.083 (1) Šfrom the plane through the four S atoms, and also by the torsion angles about the Ni-S bonds, implies a folded conformation for the chelate ring.