Indirect effects of oral tolerance to ovalbumin interfere with the immune responses triggered by Schistosoma mansoni eggs

The objective of the present study was to investigate whether the injection of a tolerated protein (indirect effects) affects the formation of granulomas around Schistosoma mansoni eggs trapped in the lungs after intravenous (iv) injection into normal (noninfected) C57BL/6 mice (6 animals per group). To induce oral tolerance to chicken egg ovalbumin a 1/5 dilution of egg white in water was offered ad libitum in a drinking bottle for 3 days. Control mice received water. After 7 days, control and experimental animals were injected iv with 2,000 S. mansoni eggs through a tail vein. In some mice of both groups the iv injection of eggs was immediately followed by intraperitoneal (ip) immunization with 10 µg of dinitrophenylated conjugates of ovalbumin (DNP-Ova) emulsified in complete Freund's adjuvant (CFA) or only CFA; 18 days later, mice were bled and killed by ether inhalation. The lungs were fixed in formalin and embedded in paraffin. Serial sections of 5 µm were stained with Giemsa, Gomori's silver reticulin and Sirius red (pH 10.2). Granuloma diameters were measured in histological sections previously stained with Gomori's reticulin. Anti-DNP and anti-soluble egg antigen (SEA) antibodies were analyzed by ELISA. In mice orally tolerant to ovalbumin the concomitant ip injection of DNP-Ova resulted in significantly lower anti-SEA antibodies (ELISA*: 1395 ± 352 in non-tolerant and 462 ± 146 in tolerant mice) and affected granuloma formation around eggs, significantly decreasing granuloma size (area: 22,260 ± 2478 to 12,993 ± 3242 µm²). Active mechanisms triggered by injection of tolerated antigen (ovalbumin) reduce granuloma formation.

Prolactin induces adrenal hypertrophy

Although adrenocorticotropic hormone is generally considered to play a major role in the regulation of adrenal glucocorticoid secretion, several reports have suggested that other pituitary hormones (e.g., prolactin) also play a significant role in the regulation of adrenal function. The aim of the present study was to measure the adrenocortical cell area and to determine the effects of the transition from the prepubertal to the postpubertal period on the hyperprolactinemic state induced by domperidone (4.0 mg kg-1 day-1, sc). In hyperprolactinemic adult and young rats, the adrenals were heavier, as determined at necropsy, than in the respective controls: adults (30 days: 0.16 ± 0.008 and 0.11 ± 0.007; 46 days: 0.17 ± 0.006 and 0.12 ± 0.008, and 61 days: 0.17 ± 0.008 and 0.10 ± 0.004 mg for treated and control animals, respectively; P < 0.05), and young rats (30 days: 0.19 ± 0.003 and 0.16 ± 0.007, and 60 days: 0.16 ± 0.006 and 0.13 ± 0.009 mg; P < 0.05). We selected randomly a circular area in which we counted the nuclei of adrenocortical cells. The area of zona fasciculata cells was increased in hyperprolactinemic adult and young rats compared to controls: adults: (61 days: 524.90 ± 47.85 and 244.84 ± 9.03 µm² for treated and control animals, respectively; P < 0.05), and young rats: (15 days: 462.30 ± 16.24 and 414.28 ± 18.19; 60 days: 640.51 ± 12.91 and 480.24 ± 22.79 µm²; P < 0.05). Based on these data we conclude that the increase in adrenal weight observed in the hyperprolactinemic animals may be due to prolactin-induced adrenocortical cell hypertrophy.

One-year follow-up of the effects of sildenafil on pulmonary arterial hypertension and veno-occlusive disease

We hypothesized that chronic oral administration of the phosphodiesterase-5 inhibitor sildenafil could improve the exercise capacity and pulmonary hemodynamics in patients with pulmonary arterial hypertension (PAH) on the basis of previous short-term studies. We tested this hypothesis in 14 subjects with PAH, including seven patients with the idiopathic form and seven patients with atrial septal defects, but no other congenital heart abnormalities. Patients were subjected to a 6-min walk test and dyspnea was graded according to the Borg scale. Pulmonary flow and pressures were measured by Doppler echocardiography. Patients were given sildenafil, 75 mg orally three times a day, and followed up for 1 year. Sildenafil therapy resulted in the following changes: increase in the 6-min walk distance from a median value of 387 m (range 0 to 484 m) to 462 m (range 408 to 588 m; P < 0.01), improvement of the Borg dyspnea score from 4.0 (median value) to 3.0 (P < 0.01), and increased pulmonary flow (velocity-time integral) from a median value of 0.12 (range 0.08 to 0.25) to 0.23 (range 0.11 to 0.40; P < 0.01) with no changes in pulmonary pressures. In one patient with pulmonary veno-occlusive disease diagnosed by a lung biopsy, sildenafil had a better effect on the pulmonary wedge pressure than inhaled nitric oxide (15 and 29 mmHg, respectively, acute test). He walked 112 m at baseline and 408 m at one year. One patient died at 11 months of treatment. No other relevant events occurred. Thus, chronic administration of sildenafil improves the physical capacity of PAH patients and may be beneficial in selected cases of veno-occlusive disease.

Psykiatriatieteen juuria etsimässä

Kirjallisuusarvostelu

Le Petit journal. Supplément du dimanche

1899/09/24 (Numéro 462).

L'Écho de Paris

1885/06/16 (Numéro 462).

Biblia sacra.

Avec prologues et arguments. Genesis (7v), etc. — Oratio Manasse (167) ; Esdras I-III (167v), etc. — Macchab. I-II, avec prologues de RABAN MAUR (353v, 354). — Evang. Matthaei (377), etc. — XIV Epist. Pauli (421v) ; Actus Apost. (448v) ; VII Epist. canon. (462) ; Apocalypsis (467v). — Interpretationes nominum hebraicorum : « Aaz, apprehendens... — ... consiliatores eorum. » (473v). — « Ordo librorum presentis voluminis. » (513v).