Transfusion-related acute lung injury after the infusion of IVIG

BACKGROUND: Transfusion-related acute lung injury (TRALI) is a well-characterized, serious complication of blood component therapy in hospitalized patients. The signs and symptoms are often attributed to other clinical aspects of a patient's condition, and therefore TRALI may go unrecognized. IVIG is a pooled plasma derivative commonly used in the outpatient setting. Respiratory complications of IVIG infusion have typically been attributed to volume overload or allergic and vasomotor reactions. TRALI has never been documented to occur after IVIG infusion. CASE REPORT: A 23-year-old man with multifocal motor neuropathy developed noncardiogenic pulmonary edema 6 hours after receiving 90 g of IVIG by a rapid-infusion protocol. He fully recovered in 5 days with nasal oxygen and bed rest. Granulocyte-associated IgG was detected in his blood 14 and 27 weeks after the event. The lots of IVIG that he received were found to contain a low-titer, panreactive, granulocyte antibody, mostly IgG. CONCLUSION: This is the first documented case of TRALI after IVIG infusion. An autoimmune syndrome, including autoantibody-coated granulocytes, may have been a priming stimulus for granulocyte interaction with pulmonary capillary endothelium. Rapid infusion of a large quantity of granulocyte antibody may have precipitated TRALI. A pooled plasma product or derivative may result in TRALI.     

Chlamydial infection of mothers and their infants.

In 340 women, cultured prospectively during their pregnancies, the rate of infection with Chlamydia trachomatis was 8.8%. The women with positive cultures tended to be younger and more often single and black than their counterparts with negative cultures. There were no statistically significant clinical differences between the two groups. Eighteen children born to Chlamydia culture-positive women and 16 born to negative women were followed for nine months to examine the potential effects of maternal infection on infant growth, development, and illness. Eleven of 18 study patients had culture or tear antibody evidence of Chlamydia infection, as opposed to one of the control subjects (P = 0.00093). Eight of these 11 had clinical conjunctivitis, and two of the eight developed pneumonia. Growth retardation and developmental abnormalities were not detected in either group. It is concluded that maternal carriage of C. trachomatis is associated with a high incidence of clinical illness in the offspring.     

Inherited human collagen lysyl hydroxylase deficiency: ascorbic acid response.

A patient is described with congenital hypotonia, lax joints, friable skin, hemorrhagic scars, high-arched palate, and borderline microcornea. Acid hydrolyzed whole skin collagen had a reduced hydroxylysine content of 0.5 residues per 1,000 as compared to 5.1 +/- 0.7 in control skin. Collagen lysyl hydroxylase in dialyzed subcellular fractions of cultured skin fibroblasts required L-ascorbate as a principal cofactor. Activity of this enzyme in cultured skin fibroblasts derived from this patient, his father, and mother were 17%, 66%, and 39% of control values, respectively. Collagen prolyl hydroxylase activity was normal. Pharmacologic amounts of oral vitamin C (4 gm/day) produced an increase and withdrawal resulted in abrupt diminution of urinary excretion of hydroxylysine. Over a two-year period the patient's wound healing and muscle strength improved and corneal diameter increased. Hydroxylysine content of the skin did not increase.     

Combined therapies to treat complex diseases: The role of the gut microbiota in multiple sclerosis

The commensal microbiota has emerged as an environmental risk factor for multiple sclerosis (MS). Studies in experimental autoimmune encephalomyelitis (EAE) models have shown that the commensal microbiota is an essential player in triggering autoimmune demyelination. Likewise, the commensal microbiota modulates the host immune system, alters the integrity and function of biological barriers and has a direct effect on several types of central nervous system (CNS)-resident cells. Moreover, a characteristic gut dysbiosis has been recognized as a consistent feature during the clinical course of MS, and the MS-related microbiota is gradually being elucidated. This review highlights animal studies in which commensal microbiota modulation was tested in EAE, as well as the mechanisms of action and influence of the commensal microbiota not only in the local milieu but also in the innate and adaptive immune system and the CNS. Regarding human research, this review focuses on studies that show how the commensal microbiota might act as a pathogenic environmental risk factor by directing immune responses towards characteristic pathogenic profiles of MS. We speculate how specific microbiome signatures could be obtained and used as potential pathogenic events and biomarkers for the clinical course of MS. Finally, we review recently published and ongoing clinical trials in MS patients regarding the immunomodulatory properties exerted by some microorganisms. Because MS is a complex disease with a large variety of associated environmental risk factors, we suggest that current treatments combined with strategies that modulate the commensal microbiota would constitute a broader immunotherapeutic approach and improve the clinical outcome for MS patients.     

Spontaneous cries can alter the physiological well-being and cerebral oxygenation of very preterm infants

Introduction

Infant crying is a major expression of distress and can occur without any exogenous stimulation. Little is known, however, about the effects of crying on physiological homeostasis in very preterm infants (VPIs).

Methods

Environmental, behavioral (video and audio recording) and physiologic (heart rate [HR], respiratory rate [RR], and systemic [SaO₂] and regional cerebral oxygenation [rSO₂]) parameters were prospectively evaluated over 10 h in 18 VPIs (median gestational age, 28 [27–31] weeks). Only episodes of “spontaneous” and isolated cries were analyzed. Changes in parameters were compared over 5-second periods between baselines and 40 s following the onset of crying. Two periods were distinguished: 0–20 s (a) and 20–40 s (b). Minimal and/or maximal values in these periods were also compared to the baseline.

Results

Of the 18 VPIs initially studied, 13 (72%) presented crying episodes (CE). They experienced 210 “spontaneous” and isolated CE, with a median of 9 [range, 1–63] CEs per child. Physiological values varied significantly from the baseline with mainly a mean decrease in HR of − 4.8 ± 5.3 beats/min (b) after an initial mean increase of + 2.6 ± 2.0 beats/min (a); a mean decrease in RR of − 3.8 ± 4.8 cycles/min (a), followed by a mean increase of + 5.6 ± 7.3 cycles/min (b) and mean unidirectional decreases in SaO₂ and rSO₂ (minimal values) of − 1.8 ± 2.3% and − 2.5 ± 3.0%, respectively.

Conclusion

Spontaneous cries can alter the homeostasis of VPIs. Their possible adverse consequences and high occurrence emphasize the need for better prevention and response to them.     

Early identification of the risk for free radical-related diseases in preterm newborns

Background

Despite recent advances in preterm newborns healthcare, perinatal pathologies and disabilities are increasing. Oxidative stress (OS) is determinant for the onset of an unbalance between free radicals (FRs) production and antioxidant systems which plays a key role in pathogenesis of pathologies such as retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), grouped as ‘free radical-related diseases’ (FRD).

Aim

This study tests the hypothesis that OS markers levels in cord blood may predict the onset of FRD pathologies.

Patients and methods

168 preterm newborns of GA: 24-32 weeks (28.09 ± 1.99); and BW: 470-2480 gr (1358.11 ± 454.09) were consecutively recruited. Markers of potential OS risk (non-protein bound iron, NPBI; basal superoxide anion, BSA; under stimulation superoxide anion, USSA) and markers of OS-related damage (total hydroperoxides, TH; advanced oxidation protein products, AOPP) were assessed in cord blood. Associations between FRD onset and OS markers were checked through inferential analysis (univariate logistic regression).

Results

The development of FRD was significantly associated to high cord blood levels of TH, AOPP and NPBI (respectively p = 0.000, OR = 1.025, 95%CI = 1.013-1.038; p = 0.014, OR = 1.092, 95%CI = 1.018-1.172; p = 0.007, OR = 1.26995%CI = 1.066-1.511).

Conclusions

Elevated levels of TH, AOPP and, above all, NPBI, in cord blood are associated with increased risk for FRD. OS markers allow the early identification of infants at risk for FRD because of perinatal oxidant exposure. This can be useful in devising strategies to prevent or ameliorate perinatal outcome.     

Anti-diabetic action of Punica granatum flower extract: activation of PPAR-gamma and identification of an active component

Peroxisome proliferator-activated receptor (PPAR)-gamma activators are widely used in the treatment of type 2 diabetes because they improve the sensitivity of insulin receptors. Punica granatum flower (PGF) has been used as an anti-diabetic medicine in Unani medicinal literature. The mechanism of actions is, however, unknown. In the current study, we demonstrated that 6-week oral administration of methanol extract from PGF (500 mg/kg, daily) inhibited glucose loading-induced increase of plasma glucose levels in Zucker diabetic fatty rats (ZDF), a genetic animal model for type 2 diabetes, whereas it did not inhibit the increase in Zucker lean rats (ZL). The treatment did not lower the plasma glucose levels in fasted ZDF and ZL rats. Furthermore, RT-PCR results demonstrated that the PGF extract treatment in ZDF rats enhanced cardiac PPAR-gamma mRNA expression and restored the down-regulated cardiac glucose transporter (GLUT)-4 (the insulin-dependent isoform of GLUTs) mRNA. These results suggest that the anti-diabetic activity of PGF extract may result from improved sensitivity of the insulin receptor. From the in vitro studies, we demonstrated that the PGF extract enhanced PPAR-gamma mRNA and protein expression and increased PPAR-gamma-dependent mRNA expression and activity of lipoprotein lipase in human THP-1-differentiated macrophage cells. Phytochemical investigation demonstrated that gallic acid in PGF extract is mostly responsible for this activity. Thus, our findings indicate that PPAR-gamma is a molecular target for PGF extract and its prominent component gallic acid, and provide a better understanding of the potential mechanism of the anti-diabetic action of PGF.