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Biomedical subjects

E del Pozo

Publications and source records attributed to E del Pozo.

At least 37 records · Page 2Linked to original sources
PubMed1987

Suppression of growth hormone and somatomedin C by long-acting somatostatin analog SMS 201-995 in type I diabetes mellitus.

The effect of a new long-acting somatostatin analog SMS 201-995 (SMS) on hormonal mechanisms controlling the glucose metabolism was tested in 8 type I diabetics over a 3-day period. In addition to dietary measures and conventional insulin therapy, the patients received a subcutaneous dose of 50 micrograms SMS three times daily for 3 days. Serum growth hormone (GH) was measured at various intervals throughout the investigational period. Glucagon, somatomedin C (SM-C), triiodothyronine, thyroxine, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin (PRL) were also determined before and at the end of the therapy with SMS. Basal GH and plasma SM-C had decreased significantly (p less than 0.05 and p less than 0.01, respectively) by the 3rd day. In all cases the insulin requirements could be reduced (mean 28%) without deterioration of the metabolic control. Moreover, blood glucose profiles showed a tendency to lower postprandial peaks after SMS treatment. Glucagon, triiodothyronine, thyroxine, LH, FSH and PRL showed no significant changes. No side effects or alterations in laboratory chemistries were recorded. Dampening of glucose oscillations and counterregulatory mechanisms, and reduction of insulin dosage by SMS may enable a better control of unstable diabetes. Its slow plasma clearance and long action compared to the native peptide will warrant the use of this analog as a additive to standard diabetes therapy in more prolonged trials.

Adult↗
PubMed1987

Medical treatment of acromegaly with SMS 201-995, a somatostatin analog: a comparison with bromocriptine.

We studied the effects of acute and chronic sc administration of SMS 201-995 (SMS), a long-acting somatostatin analog, in acromegalic patients. The results were compared with those obtained in the same patients treated with oral bromocriptine (Brc). A single dose of 50 micrograms SMS administered to 28 patients induced a more rapid, greater, and more prolonged reduction in plasma GH levels than did 2.5 mg Brc. Chronic treatment [60-330 days; mean 208 +/- 23 (+/- SEM)] with SMS (100-300 micrograms/day) induced in 16 patients a significantly greater decrease in mean plasma GH and somatomedin-C levels than did 20 mg Brc. Combined treatment with the 2 agents had an additional effect. The clinical and metabolic parameters of acromegaly dramatically improved in all patients whose plasma GH and somatomedin-C levels decreased even if they were not normalized by SMS. Reduction in tumor size occurred in 3 of the 10 patients examined by computed tomography before and during SMS treatment. We conclude that SMS is more effective than Brc and that the 2 drugs may be complementary in the medical treatment of acromegaly.

Acromegaly↗
PubMed1987

SMS 201-995 induces a continuous decline in circulating growth hormone and somatomedin-C levels during therapy of acromegalic patients for over two years.

Ten acromegalic patients, four previously untreated, were studied before and at regular intervals during treatment with the long-acting somatostatin analog SMS 201-995 (200-300 micrograms daily for 2 or 3 sc injections for 16-108 weeks). All patients had rapid clinical improvement, with disappearance of excessive perspiration, paresthesias, and headache within the first 6 weeks of therapy. The mean 24-h serum GH concentrations fell from 44.0 +/- 7.8 (+/-SE) micrograms/L before to 5.9 +/- 1.0 microgram/L at the end of therapy. The GH levels from 2-6 h after the acute administration of 50 micrograms SMS 201-995 before the start of therapy correlated significantly with the mean 24-h GH concentrations after 16-108 weeks of treatment (P less than 0.05). The initially increased serum somatomedin-C (Sm-C) levels normalized in 5 of these 10 patients; the mean values were 7.3 +/- 0.9 U/mL before and 2.9 +/- 0.7 U/mL at the end of therapy. The Sm-C and mean GH levels continuously decreased during long term therapy; the concentrations after 1.5-2 yr of therapy were significantly lower than those after 6-12 months of therapy (P less than 0.01 and P less than 0.01, respectively). A slight decrease in the size of the pituitary tumor was noted by computed tomography in three of six patients. Transient clinically detectable steatorrhea occurred in two patients. Postprandial hyperglycemia occurred during therapy in eight patients, while in two patients with type 2 diabetes mellitus carbohydrate tolerance improved in one and deteriorated in the other. SMS 201-995 is a highly effective medical treatment for acromegaly. Clinically improvement occurs rapidly, and the inhibition of serum GH and Sm-C levels persisted even after more than 1 yr of therapy. No important subjective side-effects were noted. SMS 201-995 is an excellent drug in patients in whom acromegaly persists after surgery and for interim treatment to shorten the period of clinical activity after irradiation.

Acromegaly↗
PubMed1986

Long-term treatment of acromegaly with the somatostatin analogue SMS 201-995 over 6 months.

This study examined the effects of the long-acting selective mini somatostatin analogue (SMS) 201-995 in two acromegalic patients who were treated for 3 and 6 months, respectively. During treatment the mean growth hormone levels (25.3 and 20.8 ng/ml vs 5.9 and 10.6 ng/ml) and somatomedin C levels (6.2 and 6.2 IU/ml vs 3.3 and 3.8 IU/ml) decreased and the patients reported an improvement in their symptoms. The main side effect was an increase in stool fat excretion which did exceed the normal range (less than 7 g/day) in one patient. Five acromegalics who received 2 X 50 micrograms SMS 201-995/day for 5 days showed a significant increase of stool fat excretion (1.7 vs 3.5 g/day; p less than 0.05). Fasting blood glucose levels, glucose tolerance, and glycosylated hemoglobin were not essentially effected. It is concluded that SMS 201-995 offers new possibilities in the treatment of acromegaly. The gastrointestinal and diabetogenic side effects of this substance, however, should be carefully monitored.

Acromegaly↗
PubMed1986

Pharmacokinetics of a long-acting bromocriptine preparation (Parlodel LA) and its effect on release of prolactin and growth hormone.

The pharmacokinetics and endocrine actions of a long-acting form of bromocriptine (Parlodel) were examined in a controlled study in 10 healthy volunteers receiving a single i.m. injection of 50 mg. Six further subjects took bromocriptine 1.25 mg t.i.d. for 3 days p.o. In the subjects given the slow release preparation, the plasma bromocriptine concentrations increased sharply to a maximum of 1.65 mg/l 2 h after injection. This fast release process was followed by slow clearance with a half-life of 16 days. The substance was still detectable in plasma 35 days postinjection. Plasma prolactin (PRL) fell rapidly from a mean of 5.6 ng/ml to reach significantly lower levels at 60 and 120 min. Inhibition was maintained for up to 35 days, when plasma PRL was still significantly below the values recorded at baseline and in the control group. Plasma GH peaked at 3.6 ng/ml at 120 min and subsequently declined slowly to stabilize between 1.4 and 2.2 ng/ml for about 12 h, falling to below the 1 ng/ml limit for the remainder of the study period. In contrast, individuals receiving oral bromocriptine exhibited a significant elevation following the first dose and an equivalent increment after the morning dose on Day 3. Thus, the results show a prolonged inhibitory effect on PRL of this long-acting bromocriptine preparation in parallel with its slow plasma clearance. The stimulant effect on GH secretion is short lived, presumably due to desensitisation of specific receptors.

Adult↗
PubMed1986

Inhibitory effect of bromocriptine treatment on luteinizing hormone secretion in polycystic ovary syndrome.

In order to investigate a possible common role of central dopaminergic mechanisms in the release of PRL and LH in patients with the polycystic ovary syndrome (PCO), plasma LH pulsatile profiles and the response to GnRH were studied in a group of 12 PCO patients before and after 3 months of treatment with bromocriptine, 2.5 mg twice daily. They were divided into two groups of six patients according to the occurrence or not of hyperprolactinemia (plasma PRL, 30.3 +/- 2.7 (SE) ng/ml vs. 9.5 +/- 0.8 (SE) ng/ml). Integrated LH secretion significantly decreased in hyperprolactinemic [2537 +/- 371 (SE) vs. 907 +/- 102 mIU/ml X min] as well as in normoprolactinemic (2847 +/- 460 vs. 901 +/- 152 mIU/ml X min) patients, but there was no difference in the response of the two groups. The LH increment after a bolus injection of 100 micrograms GnRH was reduced (P less than 0.01) to the same extent in both groups. These results indicate a dopaminergic component in the control of LH release in PCO patients, independent of the mechanism governing PRL secretion. Since bromocriptine reduced LH secretion, it may be useful for the management of this condition.

Bromocriptine↗
PubMed1986

A comparison among the growth hormone-lowering effects in acromegaly of the somatostatin analog SMS 201-995, bromocriptine, and the combination of both drugs.

The acute GH inhibitory effects of 50 micrograms SMS 201-995, a somatostatin analog, and 2.5 mg bromocriptine were compared in 17 acromegalic patients. SMS 201-995 suppressed plasma GH levels after 2-6 h to 5 micrograms/liter or less in 10 of these 17 patients, while bromocriptine did the same in only 5 of them. There was much variation in the responsiveness to both drugs in these patients, but the GH-lowering effect of 50 micrograms SMS 201-995 was significantly greater than that of 2.5 mg bromocriptine. SMS 201-995 and bromocriptine together significantly suppressed plasma GH levels in 2 of 3 acromegalic patients who were insensitive to both compounds when tested separately. We conclude that most acromegalic patients respond better to SMS 201-995, while a few patients are more sensitive to the GH-lowering effect of bromocriptine. In addition, the combination of SMS 201-995 and bromocriptine can be of value in a few acromegalic patients who do not respond to either drug alone.

Acromegaly↗
PubMed1986

Endocrine profile of a long-acting somatostatin derivative SMS 201-995. Study in normal volunteers following subcutaneous administration.

The pharmacokinetics and the endocrine profile of a new low molecular somatostatin derivative, SMS 201-995, were investigated in a group of 35 normal subjects. Clearance studies (n = 6) for this peptide showed a prolonged half-life in plasma, 113 min, following single sc injections of 50 or 100 micrograms. Arginine stimulation tests (n = 6) were conducted immediately and 180 min after sc injection of 50 micrograms of SMS 201-995. The stimulatory effect of arginine on GH and insulin was counteracted by the peptide at the P less than 0.001 and P less than 0.02 significance level, respectively. Delayed arginine stimulation revealed a persistent blockade of the GH release (P less than 0.02), whereas a recovery of the insulin response was observed. Plasma glucagon increments following a standard protein meal (n = 10) were significantly (P less than 0.001) inhibited by previous sc injection of 50 micrograms of SMS 202-995. Pretreatment with 50 and 100 micrograms of SMS 202-995 sc (n = 9) inhibited (P less than 0.001) the stimulatory effect of TRH (200 micrograms iv) on TSH without modifying basal levels. The injection of 100 micrograms/h during sleep completely abolished the nocturnal GH peak in 4 volunteers. No rebound rise after decline of the suppressive action on GH was recorded in any of the trials. Safety chemistries and blood coagulation studies remained normal and no side-effects or untoward reactions were recorded throughout the investigation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Acute and long-term effects of SMS 201-995 in acromegaly.

The subcutaneous administration of 50 micrograms SMS 201-995 at 0815 h in 18 acromegalic patients reduced plasma growth hormone (GH) levels from 2 to 6 h after injection from 36 +/- 2 to 7 +/- 1 microgram/l (-80 +/- 5%). Circulating GH concentrations had normalized to less than 5 micrograms/l during this period in 11 of 18 patients. Postprandial blood glucose levels after breakfast were significantly (p less than 0.01) higher after SMS administration but significantly lower (p less than 0.01) after supper. Chronic treatment of five acromegalic patients with 200-300 micrograms SMS 201-995 daily for 8-24 weeks resulted in a rapid clinical improvement in all patients and complete disappearance of the complaints in four of five patients. This was accompanied by tumour shrinkage as estimated by computerized tomography scanning in three of four patients. In parallel, mean plasma GH levels and serum somatomedin-C and phosphorus levels fell to or within the normal values. SMS 201-995 represents a new tool in the medical management of acromegaly and may become the treatment of choice, especially in patients who do not benefit sufficiently from surgery and/or radiotherapy.

Acromegaly↗
PubMed1986

Therapy of acromegaly with SMS 201-995: long-term studies.

Fourteen acromegalic patients, half of whom had been unsuccessfully treated with surgery, radiotherapy, or bromocriptine, were given the somatostatin analogue SMS 201-995 parenterally as the sole therapeutic regimen after a single administration had demonstrated suppression of serum growth hormone (GH). An impressive and sustained clinical improvement was documented in all patients, including those in whom bromocriptine had failed; most marked was the decrease in soft tissue swelling and headache and an improved performance status. GH levels decreased each time SMS 201-995 was injected but returned to basal levels within 8 h in most of the patients. With chronic therapy, 24-h mean levels were significantly suppressed, and the GH stimulability of thyrotrophin-releasing hormone and growth-hormone-releasing hormone (pl-44) was markedly reduced. Discontinuation of SMS 201-995 therapy was associated with a return of symptoms and abnormal GH dynamics. The efficacy and safety of chronically administered SMS 201-995 in active acromegaly opens new horizons for its treatment.

Acromegaly↗
PubMed1986

Somatostatin analogue SMS 201-995 in type I diabetes mellitus. Initial experience after repeated administration.

We have recently obtained encouraging short-term results after a single subcutaneous injection of the long-acting somatostatin analogue SMS 201-995 in acromegalic patients. Increased growth hormone (GH) levels may be involved in the pathogenesis of proliferative retinopathy in type I diabetes mellitus. In this study we thus investigated the effect of 3 X 50 micrograms SMS 201-995 daily on the metabolic control and hormone secretion of eight type I diabetics over a 3-day period. GH levels decreased by 32% (p less than 0.05) and somatomedin C levels by 31% (p less than 0.01) on the 3rd day of treatment compared with a control day. The insulin requirements during conventional subcutaneous insulin therapy were reduced by 28% (p less than 0.01) in seven patients without deterioration of metabolic control (mean blood glucose levels, 153.8) versus 154.7 mg/dl). Triiodothyronine, thyroxine, glucagon, prolactin, luteinizing hormone and follicle-stimulating hormone showed no significant changes. We conclude that SMS 201-995 could be an excellent tool for further clinical investigation and therapy of diabetic vascular complications.

Adult↗
PubMed1986

Therapeutic efficacy of a somatostatin analogue (SMS 201-995) in active acromegaly.

Twelve patients with active acromegaly, six of whom had not responded to previous combined surgery, radiotherapy, and bromocriptine administration, were treated with an octapeptide long-acting somatostatin analogue, SMS 201-995, given subcutaneously for up to 1 year. Growth hormone (GH) levels decreased by 50% to 90% after a single 25-micrograms SMS 201-995 injection in all patients, including two who were resistant to bromocriptine therapy. After GH values reached a nadir, they returned to preinjection values over a 12-hour period and no rebound was seen. Assessment of the GH-lowering effect of the drug at weekly intervals for the first 6 weeks and monthly thereafter disclosed no tachyphylaxis. Gradual increase of the dose from 50 to 150 micrograms daily led to a significant increase in clinical improvement. Shrinkage of the size of the pituitary tumor was documented in three of nine evaluated cases. Abdominal cramps of a transient nature not associated with diarrhea were noted in two patients but there were no other side effects. Hematological and biochemical blood and urine tests, including serum thyroxine and cortisol levels, did not reveal any abnormality during chronic treatment. This study demonstrates the safety and efficacy of SMS 201-995 in the short-term treatment of acromegaly.

Acromegaly↗
PubMed1985

Long-term treatment of acromegaly with the somatostatin analogue SMS 201-995.

We treated four patients with acromegaly for 8 to 24 weeks with SMS 201-995, the long-acting somatostatin analogue, in dosages of 100 to 300 micrograms a day given subcutaneously. A rapid amelioration of the clinical signs and symptoms and near normalization of laboratory test results occurred in all patients. Mean plasma growth hormone concentrations (+/- S.E.M.), as measured over 24 hours, fell from an initial value of 57 +/- 18 micrograms per liter to 7.5 +/- 2 micrograms per liter at the end of the investigational period. Likewise, levels of plasma somatomedin-C, which were originally elevated in all patients, dropped to the normal or nearly normal range. The suppression of insulin secretion and the resulting hyperglycemia that were observed at the beginning of treatment became less marked as therapy progressed. There was evidence of slight tumor shrinkage in three of the subjects. No side effects were recorded throughout the treatment period. These preliminary results suggest that SMS 201-995 represents an additional option for the management of acromegaly, especially in patients who do not benefit sufficiently from surgery or radiotherapy and do not respond well to treatment with dopaminergic drugs.

Acromegaly↗
PubMed1985

Effect of dopamine receptor stimulation on the inhibition of LH pulsatility by a met-enkephaline (FK 33-824).

Plasma LH fluctuations reflect pulsatile hypothalamic GnRH activity. In order to investigate a possible interaction between opiate and dopaminergic pathways in the control of LH and PRL release, a met-enkephalin analogue (FK 33-824) was administered intravenously to female volunteers at a rate of 0.01 mg/kg/h for 4 h. LH pulses as recorded by plasma measurements every 20' were significantly (p less than 0.01) inhibited whereas PRL concentrations were increased. Pre-treatment with bromocriptine, 1.25 mg b.i.d. for 3 days, counteracted the stimulatory effect of FK 33-824 on PRL secretion but the inhibitory effect on LH episodic release was not modified by this dopamine agonist. Results indicate that opiate receptor stimulation selectively depresses hypothalamic GnRH activity and enhances PRL release from pituitary lactotrops. The GnRH lowering effect does not seem to be mediated by dopaminergic mechanisms which govern PRL secretion. Also transient, opioid-induced hyperprolactinemia is not causally related to the suppression of hypothalamic GnRH activity.

D-Ala(2),MePhe(4),Met(0)-ol-enkephalin↗
PubMed1985

Management of borderline hyperprolactinemia.

Progressively increasing plasma prolactin (PRL) concentrations are currently associated with menstrual disturbances, anovulation and cessation of cyclic activity. Galactorrhea-amenorrhea in the presence of normal plasma PRL is rare, but the favorable response to bromocriptine confirms its lactogen dependency. The concept of "transient hyperprolactinemia' is analyzed and alternative explanations for the positive results of dopamine agonist therapy in this particular condition are proposed. Moderate hyperprolactinemia can be associated with luteal inadequacy and infertility. Inhibition of PRL secretion with bromocriptine can normalize luteal function and restore the ability to conceive.

Adult↗
PubMed1985

The somatostatin analog SMS 201-995 induces long-acting inhibition of growth hormone secretion without rebound hypersecretion in acromegalic patients.

The acute effect of the somatostatin analog SMS 201-995 (SMS) was investigated in eight acromegalic patients. This substance is an octapeptide [DPhe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-(ol)] that inhibits GH release in experimental animals and man. After a control day, 50 micrograms SMS were injected sc, and plasma GH and insulin and blood glucose levels were measured at multiple intervals for 24 h. GH significantly (P less than 0.001) decreased in seven of eight acromegalic patients from 30 +/- 5 (+/- SE) to an average of 10.7 +/- 4 micrograms/l from 1-10 h after drug administration. No rebound effect occurred. Postprandial blood glucose levels were significantly (P less than 0.01) higher between 2 and 4 h after SMS treatment compared with control day values, and there was a substantial reduction in insulin secretion, as estimated by the area under the curve (P less than 0.01), during the first 3 h after SMS administration. Circulating GH was not altered by SMS or the dopamine agonist mesulergine in one patient, but the combination of both substances (50 micrograms SMS, sc, and 0.5 mg mesulergine, orally) reduced GH to below 50% of basal. In vitro studies showed that 1 PM, 0.1 nM, and 10 nM SMS or natural somatostatin exerted a similar inhibitory effect (12-39% reduction; P less than 0.01 for all three strengths) on GH release by cultured human pituitary tumor cells. In conclusion, the somatostatin derivative SMS exerts a potent and prolonged inhibitory action on GH secretion and a shorter lasting suppression of insulin in acromegalic patients. Therefore, it may represent a useful tool in the chronic management of this condition.

Acromegaly↗
PubMed1984

Long-acting and selective suppression of growth hormone secretion by somatostatin analogue SMS 201-995 in acromegaly.

In 6 of 7 acromegalic patients a single subcutaneous injection of 50 micrograms of a new octapeptide somatostatin analogue (SMS 201-995) reduced serum growth hormone (GH) from 30 +/- 12 ng/ml to 1.4 +/- 0.4 (mean +/- SEM). Serum GH remained below basal concentration for 9 h. In the remaining patient who had very high basal preprandial serum GH, SMS 201-995 produced a reduction in serum GH of only 20%. Plasma glucose concentrations were increased to the upper limits of the normal range when a high-carbohydrate meal was consumed 2 h after injection. In non-diabetic patients plasma glucose did not exceed 129 mg/dl. The 40% decrease in plasma glucagon, which lasted for 7 h after SMS 201-995 injection, was not statistically significant. No side-effects and no rebound phenomenon were observed. These results suggest that SMS 201-995 may be the first somatostatin analogue suitable for the clinical management of acromegaly.

Acromegaly↗