Human detoxification of perfluorinated compounds.

There has been no proven method thus far to accelerate the clearance of potentially toxic perfluorinated compounds (PFCs) in humans. PFCs are a family of commonly used synthetic compounds with many applications, including repelling oil and stains on furniture, clothing, carpets and food packaging, as well as in the manufacturing of polytetrafluoroethylene - a non-stick surfacing often used in cookware (e.g. Teflon(r)). Some PFCs remain persistent within the environment due to their inherent chemical stability, and are very slowly eliminated from the human body due, in part, to enterohepatic recirculation. Exposure to PFCs is widespread and some subpopulations, living in proximity to or working in fluorochemical manufacturing plants, are highly contaminated. PFC bioaccumulation has become an increasing public health concern as emerging evidence suggests reproductive toxicity, neurotoxicity and hepatotoxicity, and some PFCs are considered to be likely human carcinogens. A case history is presented where an individual with high concentrations of PFCs in serum provided: (1) sweat samples after use of a sauna; and (2) stool samples before and after oral administration of each of two bile acid sequestrants - cholestyramine (CSM) and saponin compounds (SPCs). Stool samples before and after use of a cation-exchange zeolite compound were also examined. PFCs found in serum were not detected in substantial quantities in sweat or in stool prior to treatment. Minimal amounts of perfluorooctanoic acid, but no other PFCs, were detected in stool after SPC use; minimal amounts of perfluorooctanesulfonate, but no other PFCs, were detected in stool after zeolite use. All PFC congeners found in serum were detected in stool after CSM use. Serum levels of all PFCs subsequently declined after regular use of CSM. Further study is required but this report suggests that CSM therapy may facilitate gastrointestinal elimination of some PFCs from the human body.

Adenosine receptor occupancy suppresses chemoattractant-induced phospholipase D activity by diminishing membrane recruitment of small GTPases.

Adenosine (Ado) is an important autocrine modulator of neutrophil functions. In this study, we determined the effects of endogenous Ado on fMet-Leu-Phe (fMLP)-induced phospholipase D (PLD) activity in neutrophils. The removal of extracellular Ado by Ado deaminase (ADA) or the blockade of its action by the A2a receptor antagonists 8-(3-chlorostyryl) caffeine (CSC) or CGS15943 markedly increased fMLP-induced PLD activation. The concentration-dependent stimulatory effects of CSC and CGS15943 were abolished by a pretreatment of neutrophil suspensionswith ADA. In contrast, the selective A2a receptor agonist CGS21680 suppressed fMLP-induced PLD activation. Furthermore, inhibition by CGS21680 of fMLP-induced PLD activity was reversed by CSC or CGS15943. The removal of Ado by ADA or the blockade of its action by CSC or CGS15943, markedly increased the membrane recruitment of cytosolic protein kinase Calpha (PKCalpha), RhoA, and ADP-ribosylation factor (ARF) in response to fMLP. As shown for PLD activity, the stimulatory effect of Ado receptor antagonists on PLD cofactors translocation was abolished by a pretreatment of the cells with ADA. Moreover, the membrane translocation of both PKCalpha, RhoA, and ARF in response to fMLP was attenuated by CGS21680 and this effect of the A2a receptor agonist was antagonized by CSC or CGS15943. These data demonstrate that Ado released by neutrophils in the extracellular milieu inhibits PLD activation by blocking membrane association of ARF, RhoA, and PKCalpha through Ado A2a receptor occupancy. (Blood. 2000;95:519-527)

Role of angiotensin-converting enzyme inhibition in glucose metabolism and renal injury in diabetes.

The role of angiotensin-converting enzyme (ACE) inhibition in glucose metabolism and renal injury in diabetes has been extensively investigated in diabetic humans, as well as in animal models of diabetes. Accumulated data indicate that ACE inhibitors have either no adverse effect on glucose control or insulin sensitivity or may even improve them. ACE inhibitors also appear to have neutral or positive effects on lipid metabolism. The variability of results between studies may relate to differences in experimental design, the degree of glycemia or insulin resistance, potassium balance, and dose or duration of ACE inhibitor treatment, among others. In contrast, ACE inhibitors have proved effective in limiting proteinuria and retarding renal function loss in insulin-dependent diabetes mellitus (IDDM) or non-insulin-dependent diabetes mellitus (NIDDM) patients. In rats with experimental or spontaneous diabetes, ACE inhibitors also reduce proteinuria and limit glomerular as well as tubulointerstitial damage, independent of their effects on systemic arterial pressure. How ACE inhibitors limit renal injury in diabetes is not entirely clear, but hemodynamic and nonhemodynamic mechanisms may be involved. Increasing evidence suggests that the intrarenal renin-angiotensin system (RAS) may be altered or activated in the diabetic kidney. Such activation may be specifically inhibited by ACE inhibitors and may explain the superiority of this class of agents over other antihypertensive agents in reducing proteinuria and slowing the progression of diabetic nephropathy.

Relationships between heart rate and heart rate variability: study in conscious rats.

Heart rate (HR) and heart rate variability (HRV) are risk markers in cardiac disease. HRV is also an index of the sympathovagal modulation of heart rate. Their relations have been rarely analyzed. We aimed to study such relations in normal adult conscious rats by using a novel bradycardic agent, a sinus node inhibitor, S-16257. Placebo-drug crossover designs were used while monitoring HR with telemetry and analyzing HRV in both time and frequency domains. S-16257 (2 mg/kg; n = 10) decreased HR by 29% and markedly increased HRV in parallel. By using various combinations of S-16257, atropine (2 mg/kg), and propranolol (4 mg/kg), a positive relation was shown between RR interval and various indexes of HRV: the slower the HR, the greater the HRV. Nevertheless, there is one exception to this correlation. When S-16257 was associated with both atropine and propranolol, the deep bradycardia was accompanied by a reduction of HRV, which indicates that the physiologic negative correlation between HR and HRV is not an intrinsic property of the pacemaker but is highly dependent on the two components of the autonomic system.

Long-term effects of perindopril on metabolic parameters and the heart in the spontaneously hypertensive/NIH-corpulent rat with non-insulin-dependent diabetes mellitus and hypertension.

The spontaneously hypertensive/NIH-corpulent (SHR/N-cp) rat is a genetic model that exhibits both non-insulin-dependent diabetes mellitus (NIDDM) and hypertension. To determine the impact of long-term treatment with the long-acting angiotensin-converting enzyme (ACE) inhibitor perindopril (PE) on the glucose metabolism, lipid levels, and heart in this model, studies were performed in three groups of SHR/N-cp rats maintained on a diet containing 54% carbohydrate with 18% sucrose and 36% starch. One group of obese rats received PE (0.5 to 1.0 mg/kg body weight/d) for 3 to 4 months, a second group of obese rats received no treatment, and a third group of lean rats were used as controls. The mean systolic blood pressure (SBP) increased gradually in both untreated obese and lean rats, with lean animals showing slightly higher levels compared with untreated obese rats. By contrast, SBP was reduced to normal levels in PE-treated obese rats throughout the treatment period. Compared with lean rats, obese rats showed significantly higher body weight and fasting serum levels of glucose, insulin, total cholesterol (TC), and triglyceride (TG). However, no significant differences were observed in these metabolic parameters between PE-treated and untreated obese rats. Plasma renin activity measured at the end of the treatment period was significantly higher in PE-treated rats compared with untreated obese and untreated lean rats. The mean heart weight and left ventricular weight, expressed in absolute terms or indexed to body weight, were significantly lower in PE-treated versus untreated obese and untreated lean rats. To further determine whether glucose metabolism is directly affected by PE treatment, in vitro glycogen synthesis was evaluated in isolated soleus muscles obtained from three additional groups of animals. The basal rate of muscle glycogen synthesis was significantly lower in obese compared with lean rats (P < .05), but did not differ between PE-treated and untreated obese rats. Maximal insulin-stimulated glycogen synthesis increased threefold in PE-treated obese rats, but this increase did not differ from the increases observed in untreated obese and lean rats. In conclusion, the present study shows that long-term PE treatment in obese SHR/N-cp rats with NIDDM and hypertension effectively controlled systemic arterial pressure and resulted in a significant reduction in left ventricular weight. However, these favorable effects of PE were not associated with significant improvement in glucose tolerance, hyperinsulinemia, and hyperlipidemia in this model. PE also had no direct stimulatory effects on either basal or insulin-mediated glycogen synthesis in the isolated soleus muscle of obese rats, perhaps because of the severe insulin-resistant state of the animals. Our results support the clinical observations that antihypertensive therapy with ACE inhibitors has neutral effects on glucose metabolism and insulin sensitivity in patients with combined hypertension and NIDDM.

Perindopril ameliorates glomerular and renal tubulointerstitial injury in the SHR/N-corpulent rat.

We compared the effects of long-term treatment with the angiotensin-converting enzyme inhibitor perindopril and triple therapy (hydrochlorothiazide, reserpine, and hydralazine) on the metabolic and renal features in the SHR/N-corpulent (cp) rat, a genetic model of non-insulin-dependent diabetes mellitus and hypertension. Obese male SHR/N-cp rats (4 to 6 weeks old) were fed a 54% carbohydrate diet containing 18% sucrose and 36% starch. After 2 months on the diet, rats were assigned to one of three groups: one group (n=8) received perindopril (PE); the second group (n=8) received triple therapy (TT); and the third group (n=8) did not receive therapy. Treatment was maintained for 3 to 4 months. Body weight, food intake, and fasting levels of serum glucose and insulin did not differ among the three groups. Control rats exhibited progressive proteinuria in parallel with the rise in systolic blood pressure (SBP). Both PE and TT equally lowered SBP to normal levels and reduced proteinuria in treated rats. However, the reduction of proteinuria was greater and more sustained with PE than with TT (P<.05), whereas the effect of TT on proteinuria was delayed. Plasma renin activity was increased in PE and TT rats compared with control rats (P<.02). Semiquantitative analysis of renal lesions showed that the percentage of glomeruli with mesangial expansion and sclerosis and the tubulointerstitial score (an index of severity of tubulointerstitial lesions, namely tubular atrophy, inflammatory cellular infiltrates, and interstitial fibrosis) was reduced in both PE and TT rats. However, the reduction of glomerulosclerosis and tubulointerstitial lesions was greater in PE than in TT rats (P<.01). The percentage of glomerular sclerosis was positively correlated with the severity score of tubulointerstitial lesions (r=.60, P<.01). We conclude that PE is more effective than TT in halting the progression of proteinuria in the SHR/N-cp rat with non-insulin-dependent diabetes mellitus and hypertension. The antiproteinuric effect of PE is associated with significant reduction in glomerulosclerosis and tubulointerstitial lesions, independent of the effect of treating hypertension.

Heart rate and heart rate variability, a pharmacological target.

Heart rate varies with respiration, blood pressure, emotion, etc., and heart rate variability (HRV) is presently one of the best indices to predict fatal issues in cardiac failure and after myocardial infarction. HRV depends on various reflexes. In addition, parallel studies of HRV and the myocardial adrenergic and muscarinic transduction system in experimental models of cardiac hypertrophy (CH) have suggested that the myocardial phenotype at the sinus-node level may also play a role. A transgenic strain of mice with atrial overexpression of the beta 1-adrenergic receptors was generated with attenuated HRV, which demonstrates that the phenotype itself is a determinant of HRV. HRV is explored by noninvasive techniques, including simple determination of the standard error of the mean, time-domain analysis, and Fourier transformation. We recently developed a time and frequency domain method of analysis, the smoothed pseudo-Wigner-Ville transformation, which allows better exploration of nonstationarity. Nonlinear methods have also been applied due to the extreme complexity of the biological determinants, and have provided evidence of a chaotic attractor in certain conditions. It is proposed that in steady state a very simple process, which is not completely deterministic, could better explain intermit interval regulations than chaotic behavior. In contrast, under extreme circumstances the regulation proceeds using chaotic behavior. Arrhythmias and HRV can be quantitated in 16-month-old unanesthetized spontaneously hypertensive rats (SHR). Ventricular premature beats are more frequent in SHR than in age-matched controls; they disappear after converting enzyme inhibition (CEI) relative to the reduction of both cardiac hypertrophy and ventricular fibrosis. HRV is attenuated in SHR, as it is in compensatory CH in humans. When CH is prevented, HRV returns to normal. CEI is therefore antiarrhythmic. Another pharmacological application of this concept concerns the bradycardic agents that may improve HRV.

Protective effect of nifedipine against cytotoxicity and intracellular calcium alterations induced by acetaminophen in rat hepatocyte cultures.

Alteration of calcium homeostasis has been proposed to play a major role in cell necrosis induced by a variety of chemical agents such as acetaminophen (APAP). In this study, a potential protective effect of the dihydropyridine calcium channel blocking agent, nifedipine, was investigated in vitro on acetaminophen-induced hepatocyte damage. Rat hepatocytes were exposed during 20 hours to various concentrations of APAP (0.50 to 4.00 mM). The following metabolic and functional parameters were investigated: -lactate dehydrogenase (LDH) release as an indicator of plasma membrane integrity, -cell viability evaluated by the colorimetric MTT assay, and intracellular calcium concentration as evaluated by two fluorimetric methods: a scanning laser cytometer using indo-1-AM as fluorescent probe and a fluorescence plate reader using fluo-3-AM as calcium indicator. Incubation of hepatocytes with APAP alone in the range 0.50 to 4.00mM resulted in a dose-response relationship with regard to LDH release (243% to 750% of control) and to the loss of cell viability (0 to 67% of control). Moreover these results were correlated with a significant increase in cytosolic calcium content (189 to 406 nM). Nifedipine treatment prior to APAP exposure, partially prevented LDH release, the plasma membrane blebbing, and thereby the loss of viability. In addition, intracellular calcium level progressively returned within the limits of the control values with increasing concentrations of nifedipine. It can be concluded that, in vitro conditions, nifedipine pretreatment exhibits a preventive effect against acetaminophen hepatocyte injury.

Protection against gentamicin nephrotoxicity by daptomycin in nephrectomized rats.

Daptomycin was previously shown to reduce gentamicin renal toxicity and this toxicity was not delayed by the concomitant injection of daptomycin (Thibault N., L. Grenier, M. Simard, M. G. Bergeron, and D. Beauchamp, Antimicrob. Agents Chemother., 38 1027-1035 (1994)). The protective effect of daptomycin against gentamicin toxicity was evaluated in 96 female Sprague-Dawley rats. Normal and nephrectomized rats were treated with saline (NaCl, 0.9%), gentamicin (30 mg/kg/12 hrs, i.p.), daptomycin (10 mg/kg/12 hrs, s.c.) or with a combination of daptomycin plus gentamicin during 4 and 10 days. On day 4, gentamicin and daptomycin cortical levels were higher in nephrectomized gentamicin-daptomycin-treated rats (p < 0.05) as compared to all other groups. The accumulation of gentamicin or daptomycin in nephrectomized gentamicin-daptomycin-treated or gentamicin-saline-treated rats was higher on day 4 (p < 0.01) than on day 10. Other parameters such as the sphingomyelinase activity in the renal cortex, the serum creatinine, and the histopathology showed significantly fewer changes in daptomycin-gentamicin-treated rats as compared to animals given gentamicin alone. On the other hand, the protection of daptomycin was less extensive in nephrectomized rats as compared to normal rats. Daptomycin and gentamicin were localized in the lysosomes of proximal tubular cells of animals treated with daptomycin and gentamicin given alone or in combination. These results suggest that daptomycin protects against gentamicin toxicity in nephrectomized rats but to a lesser extent than in normal rats.

Scanning laser cytometry: alterations induced by cholestatic agents in isolated rat hepatocyte couplets.

Scanning laser cytometry, an analytic technique that provides an accurate fluorescent measurement in adherent cells, was used to study cholestatic mechanisms in isolated rat hepatocyte couplets (IRHC). Treatment of IRHC with cholestatic compounds induced a pericanalicular F-actin accumulation and an increase in cytosolic free calcium. These data obtained with a scanning cytometer used in conjunction with an in vitro model representing the primary secretory unit suggest that abnormalities of pericanalicular F-actin filaments and calcium homeostasis play a key role in cholestasis. Considering the necessity for the development of mechanistic studies in toxicology, this technique should prove to be an outstanding tool.

Attenuation by daptomycin of gentamicin-induced experimental nephrotoxicity.

Previously, daptomycin was shown to reduce tobramycin nephrotoxicity in vivo (D. Beauchamp, M. Pellerin, P. Gourde, M. Pettigrew, and M. G. Bergeron, Antimicrob. Agents Chemother. 34:139-147, 1990; C. A. Wood, H. C. Finkbeiner, S. J. Kohlhepp, P. W. Kohnen, and D. C. Gilbert, Antimicrob. Agents Chemother. 33:1280-1285, 1989). Female Sprague-Dawley rats were treated with saline (NaCl, 0.9%), daptomycin (10 mg/kg of body weight every 12 h, subcutaneously), gentamicin (30 mg/kg/12 h, intraperitoneally) or with a combination of daptomycin plus gentamicin over a 10-day period. Animals were killed 4, 10, and 20 days after the end of treatment. Four days after the end of drug administration, gentamicin and daptomycin levels in the renal cortices of animals treated with the combination of daptomycin and gentamicin were significantly higher than in those of rats given gentamicin or daptomycin alone (P < 0.01). Despite the higher cortical concentrations of gentamicin, rats given the combination of gentamicin and daptomycin had less reduction in renal cortex sphingomyelinase activity, less evidence of regeneration of cellular cortical cells ([3H]thymidine incorporation into cortex DNA), lower creatinine concentration in serum, and less histopathologic evidence of injury than rats given gentamicin alone. By immunogold technique, both daptomycin and gentamicin were localized to the lysosomes of proximal tubular cells, regardless of whether animals received the drugs alone or in combination. Interestingly, myeloid body formation occurred in both those animals given gentamicin alone and those given daptomycin plus gentamicin. No significant changes were observed for all groups between 10 and 20 days after the end of therapy, suggesting that the toxicity of gentamicin was not delayed by the concomitant injection of daptomycin. The results confirm that daptomycin can attenuate experimental gentamicin nephrotoxicity.

Effect of tauroursodeoxycholate on actin filament alteration induced by cholestatic agents. A study in isolated rat hepatocyte couplets.

The mechanism of the protective effect of ursodeoxycholic acid in cholestatic liver diseases remains unclear. Since there is evidence that alterations in the pericanalicular actin microfilament network play a major role in cholestasis, the aims of this study were (a) to determine the effect of the cholestatic agents, taurolithocholate (TLC) and erythromycin estolate (ERY), on F-actin distribution in isolated rat hepatocyte couplets and (b) to assess the effect of tauroursodeoxycholate (TUDC) and taurocholate on the modifications induced by these two compounds. F-actin was stained with fluorescein-isothiocyanate phalloidin and fluorimetric measurements were performed using a scanning laser cytometer ACAS 570. F-actin distribution was assessed in the couplets by the ratio of the pericanalicular area fluorescence/total couplet fluorescence (CF/TF). At non-cytotoxic concentrations, TLC (50, 100 microM) and ERY (10, 50, 100 microM) induced a significant accumulation of F-actin around the bile canaliculus as indicated by increased fluorescence in the pericanalicular area and by the increased CF/TF ratio compared with the controls. Electron microscopy studies showed significant alterations in bile canaliculi microvilli in couplets treated with 100 microM TLC. Only a few canaliculi showed an increase in pericanalicular microfilaments after treatment with 100 microM ERY. As assessed by scanning laser cytometry, TUDC prevented changes in F-actin distribution when it was added to the medium with taurolithocholate or erythromycin estolate at equimolar concentrations. However, the morphological changes observed by electron microscopy after treatment with TLC were not modified by co-treatment with TUDC. Taurocholate was ineffective. We conclude that (a) abnormalities of pericanalicular F-actin microfilaments occur in two different models of cholestasis, (b) tauroursodeoxycholate prevents the accumulation of pericanalicular F-actin detected by scanning laser cytometry but not the morphological changes of the canaliculus observed by electronic microscopy. Therefore, in these experimental conditions, the protective effect of TUDC appears to be partial.

[The recent evolution of fertility in Quebec: demographic and socioeconomic determinants]. / L'evolution recente de la fecondite au Quebec: facteurs demographiques, economiques et sociaux.

The purpose of this study is to assess the factors which have influenced the evolution of fertility in Quebec between 1960 and 1990, in order to have a better focus on short and middle term fertility's determining factors. A Whittaker-Henderson filter is applied to various variables presumably linked to the total fertility index in order to retrieve and isolate the trend, which then enables concentration on residuals' co-variations. A regression analysis then enables assessment of the factors' weights and the short term's influence (business cycle). Governmental incentives, notably between 1988 and 1990, appear as having contributed, as well as the overall economic conjuncture, to the observed total fertility index raise in the course of this period.

Effect of bile acids on intracellular calcium in isolated rat hepatocyte couplets.

The effects of bile acids on cytosolic free calcium ([Ca2+]i) were studied in single isolated rat hepatocyte couplets using a scanning laser cytometer and the fluorescent dye, indo-1. Cholestatic bile acids, chenodeoxycholate (CDC) and taurolithocholate (TLC) increased [Ca2+]i in a dose-dependent manner. Choleretic bile acids, tauroursodeoxycholate (TUDC) and taurocholate (TC), did not induce any change in [Ca2+]i except TC at very high doses. Treatment with TUDC added concomitantly with CDC or TLC significantly decreased the rise in [Ca2+]i induced by bile acids. These results, obtained with a polarized hepatocyte model that secretes bile, confirmed that cholestatic bile acids increase [Ca2+]i and showed that TUDC inhibits this phenomenon. These data are in agreement with a key role of intracellular calcium in cholestasis.

Actin filament alteration as a potential marker for cholestasis: a study in isolated rat hepatocyte couplets.

It has been suggested that modification of the pericanalicular microfilament network (F-actin) plays a role in cholestasis. The purposes of this study were to assess (i) the process of F-actin network reorganization in isolated rat hepatocyte couplets (IRHC) in order to define the optimal study conditions in this model, (ii) the effect of cholestatic and hepatotoxic but non-cholestatic compounds on F-actin distribution in IRHC. F-actin was stained with fluorescein isothiocyanate phalloidin and fluorimetric measurements were performed in single couplets using a scanning laser cytometer, ACAS 570. F-actin distribution was assessed by the ratio of canalicular area fluorescence/total couplet fluorescence (CF/TF). The organization of the F-actin filaments was restored in IRHC 3-6 h after plating. At non-cytotoxic concentrations, most cholestatic compounds induced a significant accumulation of F-actin around the bile canaliculus as indicated by increased fluorescence in the pericanalicular area and by the increased CF/TF ratio as compared to the controls. This accumulation could be a consequence of an inhibition of F-actin depolymerization or a higher organization of actin (redistribution, bundling or reorientation). Hepatotoxic but non-cholestatic compounds did not induce any change in pericanalicular F-actin. Abnormalities of pericanalicular F-actin therefore appear to be a specific marker of hepatocellular cholestasis.

Calcium channel blocking agents protect against acetaminophen-induced cytotoxicity in rat hepatocytes.

The effect on acetaminophen-induced cytotoxicity of three calcium channel blocking agents--diltiazem, verapamil and gallopamil--was studied in primary cultures of rat hepatocytes and compared with the chelating agent EGTA. Using the measurement of cytosolic lactate dehydrogenase (LDH) as an index of cytotoxicity, it was demonstrated that a 1-hr pretreatment with calcium channel blocking agents protected cells against acetaminophen cytotoxicity, but were less effective than EGTA. These data suggest that influx of extracellular Ca2+ into the cells could have a role in the genesis of hepatocyte injury by acetaminophen.

[Quebec's 1986 population figure. Comparing the census with Quebec's health insurance file]. / L'effectif de la population du Quebec en 1986. Une comparaison entre le recensement et le fichier de l'assurance-maladie.

The author compares the 1986 population figures obtained through the Canadian census to figures from Quebec's health insurance file. The difference between the two "is very close to the one implied by the estimated rate of undercounting. This paper explains the functioning of the file and how it may be used for demographic purposes, and provides some results by age and sex as well as by region." (SUMMARY IN ENG AND SPA)

[Comments on the article by Henripin and Pelletier, "A quarter of Quebecois born outside Quebec 100 years from now?": a statistical genocide]. / Commentaires sur l'article d'Henripin et Pelletier "Un quart d'allogenes au Quebec dans 100 ans?": un genocide statistique.

PIP: The author comments on an article by Jacques Henripin and Louis Pelletier concerning the implications of current demographic trends for the population of the province of Quebec. He critically evaluates their methodology, calculations, hypotheses, and conclusions. A reply by Henripin and Pelletier is included (pp. 145-64).^ieng

[A presentation of the provisional forecasts of the population of Quebec, 1981-2001]. / Presentation des perspectives provisoires de la population du Quebec, 1981-2001

PIP: Some preliminary forecasts for the population of the province of Quebec from 1981 to 2001 are presented. These forecasts have been developed by the Statistical Bureau of Quebec and take into account recent trends in fertility, mortality, and migration. A series of multi-regional projections currently being developed for the province is also described.^ieng